The Association between Adiponectin Single Nucleotide Polymorphisms and Side Effects of Isotretinoin in Acne Patients

Garba, Munir; Khabour, Omar F.; Alzoubi, Karem H.; Abu-Siniyeh, Ahmed; Al-Qarqaz, Firas

doi:https://doi.org/10.1155/2020/3176521

Dermatology Research and Practice

On this page

Abstract Introduction Materials and Methods Results Discussion Data Availability Conflicts of Interest Acknowledgments References Copyright Related Articles

Research Article | Open Access

Volume 2020 | Article ID 3176521 | https://doi.org/10.1155/2020/3176521

The Association between Adiponectin Single Nucleotide Polymorphisms and Side Effects of Isotretinoin in Acne Patients

Munir Garba,¹Omar F. Khabour,¹Karem H. Alzoubi,²Ahmed Abu-Siniyeh,³and Firas Al-Qarqaz⁴

Academic Editor: E. Helen Kemp

Received13 Jan 2020

Revised27 Mar 2020

Accepted16 Apr 2020

Published29 Apr 2020

Abstract

Background. Acne is a common condition of pilosebaceous follicle especially among young. Clinically, the most used medication in the treatment of moderate to severe acne is oral isotretinoin. However, interindividual variability in therapeutic response to isotretinoin and many side effects such as musculoskeletal pain, headache, and alteration in lipid profile can be seen with this treatment. Aim. In this study, the effect of genetic polymorphisms, rs2241766 and rs1501299, of the adiponectin gene was investigated in relation to the side effects of isotretinoin-treated young adult acne patients (n = 230). Methods. Several biochemical parameters were measured at baseline and after treatments with isotretinoin. The ADIPOQ gene SNPs, rs2241766 and rs1501299, were genotyped in 230 patients. Results. Alterations in lipid profile with a significant increase of ALT () were detected after isotretinoin treatment. Moreover, percentage change in HDL following isotretinoin treatment was significantly associated with rs1501299 (). On the other hand, no associations between examined SNPs and side effects of isotretinoin and other lipid parameters (total cholesterol, LDL, and triglycerides) or liver function enzymes (ALT and AST) were detected. Conclusions. Current findings showed that rs1501299 of the ADIPOQ gene might be associated with changes in HDL level in acne patients following treatment with isotretinoin.

1. Introduction

Acne is a common skin condition of the pilosebaceous follicle, identified by a variety of noninflamed (comedons) and inflammatory lesions [1, 2], which primarily affects the face, upper trunk, upper arms, and back [3]. The prevalence and the severity of acne is highest among the adolescence, affecting up to 91% of males and 79 % of females of this group [4] and often persist well in adulthood [5].

The treatment of acne is based on the severity and the appearance of acne lesions [6]. Oral isotretinoin (13-cis-retinoic acid) is considered to be the most effective medication in the treatment of moderate-to-severe form of acne vulgaris [7]. However, the use of isotretinoin is associated with serious side effects [8], including depression and suicidal behavior [9, 10], elevated liver enzymes, teratogenicity, arthralgia, headache, and myalgia [11], and acute kidney injury [12, 13].

Adiponectin, a 30 KDa product of the ADIPOQ gene [14], is an abundant protein in human adipose tissues [15]. In addition, the circulating level of adiponectin in blood ranges between 2 and 30 mg/L in human [16] and about 1.5 times higher in females than males [17]. Adiponectin plays an important role in body metabolism and immune response [18, 19]. Changes in adipocytokine levels have been reported to be associated with isotretinoin medication [20–24]. For example, isotretinoin treatment of acne patients causes a significant increase in adiponectin plasma level [21, 22] and significant decrease in leptin level [22]. The ADIPOQ gene contains a number of SNPs, mostly of unknown functions. Among such SNPs are rs1501299 and rs2241766 that have been shown to be of clinical significance [25–28]. This includes modulation of disease susceptibility and the clinical outcomes to therapeutic agents [15, 26, 29, 30]. In this study, we aimed to investigate the relationship between genetic polymorphisms in the adiponectin gene, rs1501299 and rs2241766, and the side effects response in acne patients treated with 13-cis-retinoic acid among Jordanian population.

2. Materials and Methods

2.1. Study Design and Study Subjects

This cross-sectional correlation study was based on Jordanian population, in which 230 patients suffering from acne were recruited to participate in the study. Patients were enrolled in the study through collaboration with the Dermatology Department of JUST-Medical Center (Irbid), King Abdullah University Teaching Hospital (KAUH, Irbid), and Prince Hamza Hospital (Amman). All patients had established acne disease and were diagnosed on the basis of global assessments of acne. The inclusion criteria used were patients with diagnosis of acne planned to start treatment by oral isotretinoin (40 mg/day) and age 14–65 years with available information about baseline and after 1 month treatment lipid profiles and liver function tests.

The exclusion criteria were patients with habitual excessive use of alcohol, elevated lipid profile and liver enzymes (serum ALT or AST) prior to study, chronic medical illness (other than acne), and patients with concomitant and severe health problems and also any patient who refused to give informed consent. The Institutional Review Board (IRB) of Jordan University of Science and Technology approved the study.

2.2. Sample Collection and Analysis

Fasting blood sample was taken prior to the first course of isotretinoin from each subject. Initially, 3 ml of blood sample was transferred to an EDTA tube and stored at –20°C for genetic analysis. The remaining 2 ml was transferred to plain tube, and serum was obtained and stored at −20°C prior to analysis of biochemical markers. The serum levels of total cholesterol (TChol), LDL, HDL, triglyceride (TG), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in the diagnostic laboratories of KAUH using a biochemistry analyzer (Roche Diagnostics, Mannheim, Germany). The procedure was repeated from each patient a month after treatments with 13-cis-retinoic acid.

Patients enrolled in the study were interviewed using a structured questionnaire. Patient variables and data necessary for further analysis (the major demographic variables including age, gender, and education status) were recorded. Height, weight, and clinical history and current medication other than isotretinoin were obtained from the patient’s medical files. Common adverse effect profiles such as muscle pain, joint pain, headache, and nose bleeds, after oral isotretinoin therapy, as reported by the patients were recorded.

The BMI was calculated using the following equation: BMI = weight (kg)/height (m²), and patients were categorized as underweight (<18 Kgm⁻²), normal weight (14–24.9 Kgm⁻²), overweight (25–29.9 Kgm⁻²), and obese (>30 Kgm⁻²).

Assessment of depression symptoms was performed based on Arabic translated version of Beck Depression Inventory. Based on the reported symptoms, the patients were initially classified into two groups: group 1 comprised patients who did not express depression symptoms after one month of isotretinoin therapy and group 2 comprised patients with depression symptoms after isotretinoin therapy.

2.3. Genotyping of ADIPOQ Gene

The rs1501299 and rs2241766 SNPs in the ADIPOQ gene were selected based on their clinical significance on body metabolism. Genomic DNA was extracted from blood samples using the Quick-gDNA^TM MicroPrep mini kit (Zymo Research Corp, California USA), according to the manufactures protocol. PCR reaction was used to amplify the desired regions of the ADIPOQ gene at rs1501299 and rs2241766 [31, 32]. The PCR reaction was carried out using a Bio-Rad thermocycler (Bio-Rad Company) using the following protocols: precycling denaturation performed at 94°C for 7 minutes, 40 cycles denaturation for 35 seconds at 94°C, annealing for 35 seconds at 58°C, extension at 72°C for 35 seconds, and final extension for 72°C at 7 minutes. The primer sequences used for the amplification of both ADIPOQ gene SNPs, rs1501299 (F:5′GTC TAG GCC TTA GTT AAT AAT GAA TG-3′, R:5′GAG AAA GGA GAT CCA GGT AAG A-3′) and rs2241766 (F:5′-CTG AGA TGG ACG GAG TCC TTT-3′, R:5′-CCA AAT CAC TTC AGG TTG CTT-3′). After PCR, sample amplification was confirmed by gel electrophoresis, followed by detection using gene snap image accusation software (Syngene, Synoptics Ltd).

PCR-RFLP was performed on the representative of each sample. For PCR-RFLP, 10 µl of each amplified PCR product was subjected to SmaI (New England Bio Lab (UK) Ltd) restriction endonucleases digestion at 25°C incubation followed by heat inactivation at 20°C after complete digestion, and BsmI (New England Bio Lab (UK) Ltd) restriction endonucleases digestion, which recognizes the G/T allele at 65°C incubation followed by heat inactivation at 85°C. The products of digestion were resolved by electrophoresis (Bio-Rad power gel) in 3% agarose gel, stained with ethidium bromide. Gel photography was carried out using gene snap image accusation software (Syngene, Synoptics Ltd).

2.4. Statistical Analysis

Statistical analysis was carried out using SPSS software (SPSS, Chicago, IL, USA). Results were presented as mean (±SD). Comparisons were achieved using the chi-squared test, Student’s t-test, or ANOVA as appropriate. A corrected value (<0.0084) for multiple comparisons (6 variables) was considered statistically significant.

3. Results

Initially, 230 patient’s blood samples and data were obtained, but due to the incomplete information, 9 patients were excluded in the final analysis. Therefore, only 221 patients were included in this study. The demographic characteristics of the patients are presented in Table 1. Of these, 94.7% were females with female to male ratio being 9 : 1. The mean age calculated was 23.9 years old (SD, 6.498), and majority of patients were in between 21 and 30 years old. The mean BMI was 24.34 and about 90% of the patients were single and nonsmokers.

Apart from skin dryness, which was seen in all patients (a treatment effect), the most common adverse effects associated with isotretinoin treatment in the studied population were joint pain, headache, and mucosal dryness/nose bleeds. Moreover, serum levels of LDL, TChol, TG, AST, and ALT were significantly elevated one month after oral isotretinoin treatment, while serum HDL was decreased (Table 2).

The distribution of the genotypic and allelic frequencies of rs2241766 was as follows: 171 (74.35%) patients were homozygote for the wild-type TT alleles, 57 (24.78%) were heterozygote for TG alleles, and 2 (0.87%) were homozygote for GG mutant alleles. The frequency of the T allele was 399 (86.74%) while for the G allele was 61 (13.2%). This signified that the T alleles occurred more frequently than G alleles in the population studied with respect to rs2241766 of ADIPOQ.

To investigate whether rs2241766 SNPs of the ADIPOQ genotype had any effects on the alteration of lipid profile and liver enzymes after administration of isotretinoin, genotypes of rs2241766 TT and TG/GG were analyzed with respect to HDL, LDL, TG, TChol, and liver enzymes (Table 3). No significant association was found with rs2241766 genotypes and alteration of biochemical parameters, suggesting that rs2241766 might not be a contributing factor in alteration of biochemical parameters after the use of isotretinoin in acne patients.

The genotypic and allelic frequencies of rs1501299 were distributed as follows: 118 (51.3%) were homozygote for the wild-type allele GG, 112 (48.7) patients were heterozygote for GT, and none of the patients were homozygote for the mutant allele TT of rs1501299. The frequency of the G allele was 348 (75.7%) while for the T allele was (112) 24.3%.

To evaluate whether the rs1501299 genotype had any effect on alteration of lipid profile and liver enzymes, HDL, LDL, TG, TChol, AST, and ALT were analyzed with respect to the rs1501299 genotypes of acne patients Table 4. No significant association was observed between alteration of lipid profile and liver enzymes after treatments with oral isotretinoin. But, percent change by treatment of HDL showed an association with the GG and GT genotypes of rs1501299.

Each genotype was tested according to the side effect to investigate whether genetic influence of rs2241766 and rs1501299 could possibly be associated with the most common side effects of isotretinoin treatment. Neither rs2241766 nor rs1501299 polymorphism was found to be associated with the side effect of isotretinoin as shown in Table 5.

To test whether both the polymorphisms of adiponectin gene, rs2241766 and rs1501299 genotypes, are associated with depression symptoms of isotretinoin, depression status was compared among genotypes in rs2241766 TT and TG/GG (p value = 0.066) and in rs1501299 GG and GT ( value = 0.052). Therefore, neither rs2241766 nor rs1501299 is statistically associated with depression symptoms of isotretinoin.

4. Discussion

The aims of this study were to determine the most common side effects of isotretinoin treatment among Jordanian acne patients and to investigate the correlation between adiponectin gene variants, rs1501299 and rs2241766, and severity of acne and side effects of isotretinoin. The side effects of oral isotretinoin treatment are similar to some extent with that reported in other populations. In addition, the rs1501299 and rs2241766 SNPs seem to play a limited effect on side effects of isotretinoin-treated acne patients.

Isotretinoin remains the single and most important therapeutic agent that impacts virtually in all of the major etiological factors that contribute to the formation of acne [7]. The drug is capable of inducing remission after an adequate course of therapy by influencing cellular division/differentiation and significant suppression in the sebum production [33].

Regarding the adverse effect of isotretinoin on lipid and liver enzyme levels, our results were consistent with previous studies from different populations. The drug increased the cholesterol, triglyceride, and liver enzymes at a high level despite of its respectable reputation in curing acne [34−36]. On the other hand, it has been demonstrated that these high levels of lipids and liver enzymes returned normal after isotretinoin was stopped. In other retrospective study, lipids and liver enzymes were tested after 3 and 6 months following oral isotretinoin administration. Significant increases in TG, LDL, and AST levels were recorded during this period, while HDL levels were decreased. In this cohort of patients, lipids were more affected with isotretinoin than liver enzymes, and this confirms the need for regular assessment of LFTs and lipid profiles during treatment with isotretinoin as suggested by the treatment guidelines [34, 35]. These recommendations were affirmed with a later study as the results were consistent with what has been found previously, that is, variable increase in several lipid profiles when a low-dose isotretinoin was administrated by the patients. This work also emphasized on continuous monitoring of lipid profile, especially in patient with risk factors of metabolic syndrome [37]. A recent study showed that a slight-to-modest increase of lipid and liver enzyme levels always occurs when isotretinoin is taken. They came to a conclusion that frequent follow-up is not needed because the adverse effect of isotretinoin is revocable [38].

The most common reported side effects in this group of patients were mucocutaneous (dryness/nose bleeds), musculoskeletal (joint pain), and neurological (headaches). There was no statistically significant correlation with ADIPOQ gene carries of rs1501299 and rs2241766. A previous report from Turkey on 19 acne patients with 0.5 mg/kg/day convectional therapy of isotretinoin showed that the most common side effects reported were dry, chapped lips by 100 %, dry skin by 78%, nose bleeds in 11%, and fatigue in 5% of patients. None of the patients in this group reported either joint pains or muscle pains [39]. Attempt was made to correlate ADIPOQ gene carries of rs1501299 and rs2241766 and common side effects of 13-cis-retinoic acid treatment; however, the result did not reach any statistical significance.

The results showed that treatment with oral isotretinoin resulted in alteration in lipid profile and ALT and AST liver enzymes, with the marked decrease of HDL. This study found an association between the % change of HDL by treatment and GT of rs1501299, but no significant association was found between alteration in lipid profile and liver enzymes with GT and TG/GG polymorphisms of rs1501299 and rs2241766, respectively. The association between the % change of HDL and rs1501299 SNP highlights the importance of giving consideration to pharmacogenomics in oral isotretinoin treatments. The rs1501299 SNP has been shown to be associated with lipid parameters and arterial stiffness in many populations [41−44].

The present study showed that the frequency of the rs2241766 G and rs1501299 T minor alleles was 13% and 24%, respectively. The frequency of the rs2241766 G allele was similar to that of Iraqi (12%) population [40] and slightly lower than that of Egyptian (25.7%), Saudi (28.5%), and Tunisian (19%) populations [25, 41, 43]. With respect to the rs1501299 T allele, the observed frequency was higher than that reported among Saudi (1.6–4.0%) population [25] and slightly lower than that reported among Tunisian (32%) and Egyptian (31%) populations [41, 43]. A previous study showed that the rs2241766 and rs1501299 SNPs were in weak linkage disequilibrium (r² = 0.063, D’ = 0.621) [42]. However, linkage disequilibrium between these SNPs was not tested in the current investigation.

Among the limitations of the study is the relatively small sample size. In addition, genetic effects are normally affected by environmental factors. In the current study, the observed impact of rs1501299 on HDL percent change by isotretinoin treatment might be affected by diet factors. Therefore, future studies with a larger sample and controlling for diet factors are needed to confirm the present findings. Examining the impact of genetic variation on side effects of isotretinoin at the end of the treatment is strongly recommended in future studies.

In conclusion, the examined rs1501299 and rs2241766 SNPs seem to play a limited effect on the side effects of isotretinoin among acne patients. The results need to be confirmed in other populations.

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This research was funded by the Jordan University of Science and Technology, Grant number JUST-15-2015. The authors would like to thank Miss R. Hassan for her help in recruitment of subjects.

References

F. Chatzikonstantinou, A. Miskedaki, C. Antoniou, M. Chatzikonstantinou, G. Chrousos, and C. Darviri, “A novel cognitive stress management technique for acne vulgaris: a short report of a pilot experimental study,” International Journal of Dermatology, vol. 58, no. 2, pp. 218–220, 2019.
View at: Publisher Site | Google Scholar
H. Jiang and C. Li, “Common pathogenesis of acne vulgaris and atherosclerosis,” Inflammation, vol. 42, no. 1, pp. 1–5, 2019.
View at: Publisher Site | Google Scholar
F. Han, “Acne vulgaris,” The New England Journal of Medicine, vol. 380, p. 199, 2019.
View at: Publisher Site | Google Scholar
X. Huang, J. Zhang, J. Li et al., “Daily intake of soft drinks and moderate-to-severe acne vulgaris in Chinese adolescents,” The Journal of Pediatrics, vol. 204, pp. 256–262, 2019.
View at: Publisher Site | Google Scholar
T. Stringer, A. Nagler, S. J. Orlow, and V. S. Oza, “Clinical evidence for washing and cleansers in acne vulgaris: a systematic review,” Journal of Dermatological Treatment, vol. 29, no. 7, pp. 688–693, 2018.
View at: Publisher Site | Google Scholar
C. J. Roman, A. S. Cifu, and S. L. Stein, “Clinical guidelines for management of acne vulgaris-reply,” Jama, vol. 317, no. 2, p. 213, 2017.
View at: Publisher Site | Google Scholar
M. A. El-Hamd, M. A. El Taieb, H. M. Ibrahim, and S. S. Aly, “Vitamin D levels in acne vulgaris patients treated with oral isotretinoin,” Journal of Cosmetic Dermatology, vol. 18, no. 1, pp. 16–20, 2019.
View at: Google Scholar
K. R. Lumsden, A. M. Nelson, M. C. Dispenza et al., “Isotretinoin increases skin-surface levels of neutrophil gelatinase-associated lipocalin in patients treated for severe acne,” British Journal of Dermatology, vol. 165, no. 2, pp. 302–310, 2011.
View at: Publisher Site | Google Scholar
F. M. Segmiller, T. Rüther, A. Linhardt, S. Dehning, H.-J. Möller, and T. Zetzsche, “Psychosis during treatment with isotretinoin,” Therapeutic Advances in Psychopharmacology, vol. 3, no. 4, pp. 244-245, 2013.
View at: Publisher Site | Google Scholar
A. Suuberg, “Psychiatric and developmental effects of isotretinoin (retinoid) treatment for acne vulgaris,” Current Therapeutic Research, vol. 90, pp. 27–31, 2019.
View at: Publisher Site | Google Scholar
K. H. Alzoubi, O. F. Khabour, R. E. Hassan, F. Qarqaz, S. Al-Azzam, and N. Mhaidat, “The effect of genetic polymorphisms of RARA gene on the adverse effects profile of isotretinoin-treated acne patients,” Int. Journal of Clinical Pharmacology and Therapeutics, vol. 51, no. 8, pp. 631–640, 2013.
View at: Publisher Site | Google Scholar
H. M. Ahmad, “Analysis of clinical efficacy, side effects, and laboratory changes among patients with acne vulgaris receiving single versus twice daily dose of oral isotretinoin,” Dermatologic Therapy, vol. 28, no. 3, pp. 151–157, 2015.
View at: Publisher Site | Google Scholar
J. W. Marson and H. E. Baldwin, “An overview of acne therapy, Part 2,” Dermatologic Clinics, vol. 37, no. 2, pp. 195–203, 2019.
View at: Publisher Site | Google Scholar
Y. Lin, S. S. Mousa, N. Elshourbagy, and S. A. Mousa, “Current status and future directions in lipid management: emphasizing low-density lipoproteins, high-density lipoproteins, and triglycerides as targets for therapy,” Vascular Health and Risk Management, vol. 6, no. 6, pp. 73–85, 2010.
View at: Publisher Site | Google Scholar
W. L. Fang, B. Zhou, Y. Y. Wang, Y. Chen, and L. Zhang, “Analysis of adiponectin gene polymorphisms in Chinese population with systemic lupus erythematosus,” Journal of Biomedicine & Biotechnology, vol. 2010, Article ID 401537, 5 pages, 2010.
View at: Publisher Site | Google Scholar
K. Robinson, J. Prins, and B. Venkatesh, “Clinical review: adiponectin biology and its role in inflammation and critical illness,” Critical Care, vol. 15, no. 2, p. 221, 2011.
View at: Publisher Site | Google Scholar
I. M. Heid, P. Henneman, A. Hicks et al., “Clear detection of ADIPOQ locus as the major gene for plasma adiponectin: results of genome-wide association analyses including 4659 European individuals,” Atherosclerosis, vol. 208, no. 2, pp. 412–420, 2010.
View at: Publisher Site | Google Scholar
G. A. Christou and D. N. Kiortsis, “Adiponectin and lipoprotein metabolism,” Obesity Reviews, vol. 14, no. 12, pp. 939–949, 2013.
View at: Publisher Site | Google Scholar
G. Fantuzzi, “Adiponectin in inflammatory and immune-mediated diseases,” Cytokine, vol. 64, no. 1, pp. 1–10, 2013.
View at: Publisher Site | Google Scholar
K. Aydin, F. Çetinözman, G. Elcin, D. Y. Aksoy, F. Ucar, and B. O. Yildiz, “Suppressed adiponectin levels and increased adiponectin response to oral glucose load in lean women with severe acne normalizes after isotretinoin treatment,” Dermatology, vol. 233, no. 4, pp. 314–319, 2017.
View at: Publisher Site | Google Scholar
B. C. Cemil, H. H. Ayvaz, G. Ozturk et al., “Effects of isotretinoin on body mass index, serum adiponectin, leptin, and ghrelin levels in acne vulgaris patients,” Advances in Dermatology and Allergology, vol. 4, no. 4, pp. 294–299, 2016.
View at: Publisher Site | Google Scholar
A. S. Karadag, D. T. Ertugrul, Z. Takci et al., “The effect of isotretinoin on retinol-binding protein 4, leptin, adiponectin and insulin resistance in acne vulgaris patients,” Dermatology, vol. 230, no. 1, pp. 70–74, 2015.
View at: Publisher Site | Google Scholar
O. Khabour, K. Alzoubi, A. S. Firoz, and R. Al-Awad, “Association between leptin gene rs7799039 polymorphism and lipid profile changes induced by isotretinoin treatment in acne patients,” Therapeutics and Clinical Risk Management, vol. 14, pp. 949–954, 2018.
View at: Publisher Site | Google Scholar
G. Soyuduru, E. Osoy Adisen, I. Kadioglu Ozer, and A. B. Aksakal, “The effect of isotretinoin on insulin resistance and adipocytokine levels in acne vulgaris patients,” Turkish Journal of Medical Sciences, vol. 49, no. 1, pp. 238–244, 2019.
View at: Publisher Site | Google Scholar
R. N. Al-Harithy and M. H. Al-Zahrani, “The adiponectin gene, ADIPOQ, and genetic susceptibility to colon cancer,” Oncology Letters, vol. 3, no. 1, pp. 176–180, 2012.
View at: Publisher Site | Google Scholar
W. Fan, X. Qu, J. Li et al., “Associations between polymorphisms of the ADIPOQ gene and hypertension risk: a systematic and meta-analysis,” Scientific Reports, vol. 7, Article ID 41683, 2017.
View at: Publisher Site | Google Scholar
H. Hou, S. Ge, L. Zhao et al., “An updated systematic review and meta-analysis of association between adiponectin gene polymorphisms and coronary artery disease,” OMICS: A Journal of Integrative Biology, vol. 21, no. 6, pp. 340–351, 2017.
View at: Publisher Site | Google Scholar
N. Zhao, N. Li, S. Zhang et al., “Associations between two common single nucleotide polymorphisms (rs2241766 and rs1501299) of ADIPOQ gene and coronary artery disease in type 2 diabetic patients: a systematic review and meta-analysis,” Oncotarget, vol. 8, no. 31, pp. 51994–52005, 2017.
View at: Publisher Site | Google Scholar
J. Wu, Z. Liu, K. Meng, and L. Zhang, “Association of adiponectin gene (ADIPOQ) rs2241766 polymorphism with obesity in adults: a meta-analysis,” PloS One, vol. 9, no. 4, Article ID e95270, 2014.
View at: Publisher Site | Google Scholar
D. Zhang, M. Guo, W. Zhang, and X.-Y. Lu, “Adiponectin stimulates proliferation of adult hippocampal neural stem/progenitor cells through activation of p38 mitogen-activated protein kinase (p38MAPK)/glycogen synthase kinase 3β (GSK-3β)/β-catenin signaling cascade,” Journal of Biological Chemistry, vol. 286, no. 52, pp. 44913–44920, 2011.
View at: Publisher Site | Google Scholar
O. F. Khabour, L. Abu-Rumeh, M. Al-Jarrah, M. Jamous, and F. Alhashimi, “Association of adiponectin protein and ADIPOQ gene variants with lumbar disc degeneration,” Experimental and Therapeutic Medicine, vol. 8, no. 4, pp. 1340–1344, 2014.
View at: Publisher Site | Google Scholar
O. F. Khabour, M. A. Alomari, and A. A. Abu Obaid, “The Relationship of adiponectin level and ADIPOQ gene variants with BMI among young adult women,” Dermato-endocrinology, vol. 10, no. 1, Article ID e1477902, 2018.
View at: Publisher Site | Google Scholar
A. Layton, “The use of isotretinoin in acne,” Dermato-Endocrinology, vol. 1, no. 3, pp. 162–169, 2009.
View at: Publisher Site | Google Scholar
O. Kizilyel, M. S. Metin, O. F. Elmas, Y. Cayir, and A. Aktas, “Effects of oral isotretinoin on lipids and liver enzymes in acne patients,” Cutis, vol. 94, no. 5, pp. 234–238, 2014.
View at: Google Scholar
J. J. Leyden, J. Q. Del Rosso, and E. W. Baum, “The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions,” The Journal of Clinical and Aesthetic Dermatology, vol. 7, no. 2, pp. S3–s21, 2014.
View at: Google Scholar
G. Lestringant, P. Frossard, M. Agarwal, and I. Galadari, “Variations in lipid and lipoprotein levels during isotretinoin treatment for acne vulgaris with special emphasis on HDL-cholesterol,” International Journal of Dermatology, vol. 36, no. 11, pp. 859–862, 1997.
View at: Publisher Site | Google Scholar
S. Sarkar, T. Sarkar, and A. Patra, “Low-dose isotretinoin therapy and blood lipid abnormality: a case series with sixty patients,” Journal of Family Medicine and Primary Care, vol. 7, no. 1, pp. 171–174, 2018.
View at: Publisher Site | Google Scholar
A. Oktem, Y. Hayran, E. Ari, and B. Yalcin, “Minimise the regular laboratory monitoring during the systemic isotretinoin treatment: data of 704 patients with acne vulgaris,” The Journal of Dermatological Treatment, vol. 30, no. 8, pp. 813–817, 2019.
View at: Publisher Site | Google Scholar
A. Akman, C. Durusoy, M. Senturk, C. K. Koc, D. Soyturk, and E. Alpsoy, “Treatment of acne with intermittent and conventional isotretinoin: a randomized, controlled multicenter study,” Archives of Dermatological Research, vol. 299, no. 10, pp. 467–473, 2007.
View at: Publisher Site | Google Scholar
R. Aller, O. Izaola, D. Primo, and D. A. de Luis, “The effect of single-nucleotide polymorphisms at the ADIPOQ gene locus rs1501299 on metabolic parameters after 9 mo of a high-protein/low-carbohydrate versus a standard hypocaloric diet,” Nutrition, vol. 65, pp. 44–49, 2019.
View at: Publisher Site | Google Scholar
DA de Luis, O Izaola, B de la Fuente, D Primo, H Fernandez Ovalle, and E Romero, “rs1501299 Polymorphism in the Adiponectin Gene and Their Association with Total Adiponectin Levels, Insulin Resistance and Metabolic Syndrome in Obese Subjects,” Ann Nutr Metab, vol. 69, no. 3-4, pp. 226–31, 2016.
View at: Publisher Site | Google Scholar
D. E. Lowry, P. H. Fenwick, K. Roke, K. Jeejeebhoy, R. Dhaliwal, P. Brauer et al., “Variants in,” Lifestyle Genomics, vol. 11, no. 2, pp. 80–89, 2018.
View at: Publisher Site | Google Scholar
J Song, SR Yoon, and OY Kim, “T allele at ADIPOQ rs1501299 G/T polymorphism is more susceptible to the influence of circulating adiponectin on arterial stiffness in nondiabetic men,” Diabetol Metab Syndr, vol. 10, p. 44, 2018.
View at: Publisher Site | Google Scholar
M. K. Hussain, F. A. Deli, A. H. A. Algenabi, and K. H. Abdul-Rudha, “Adiponectin gene polymorphisms as a predictor for development of type 2 diabetes mellitus in Iraqi population,” Gene, vol. 662, pp. 118–122, 2018.
View at: Publisher Site | Google Scholar
L. Ghazouani, A. Elmufti, I. Baaziz, I. Chaabane, and H. Ben Mansour, “Contribution of adiponectin polymorphisms to the risk of coronary artery disease in a North-African Tunisian population,” Journal of Clinical Laboratory Analysis, vol. 32, no. 7, Article ID e22446, 2018.
View at: Publisher Site | Google Scholar
W. Zhang, L. Sun, J. Guo, X. Yu, and Y. Shi, “Family-based analysis of the adiponectin gene polymorphisms and polycystic ovary syndrome,” Zhonghua Fu Chan Ke Za Zhi, vol. 49, no. 10, pp. 758–762, 2014.
View at: Google Scholar
A. A. Mohamed, H. Omar, M. F. A. Ghaffar et al., “Single nucleotide polymorphism in adiponectin gene and risk of pancreatic adenocarcinoma,” Asian Pacific Journal of Cancer Prevention, vol. 20, no. 1, pp. 139–143, 2019.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2020 Munir Garba et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

739

Downloads

850

Citations