THADA_rs13429458 Minor Allele Increases the Risk of Polycystic Ovary Syndrome in Asian, but Not in Caucasian Women: A Systematic Review and Meta-Analysis

Sunmin Park; Meiling Liu; Ting Zhang

doi:10.1055/a-0969-1872

Hormone and Metabolic Research, Table of Contents

Horm Metab Res 2019; 51(10): 661-670
DOI: 10.1055/a-0969-1872

Endocrine Care

THADA_rs13429458 Minor Allele Increases the Risk of Polycystic Ovary Syndrome in Asian, but Not in Caucasian Women: A Systematic Review and Meta-Analysis

Sunmin Park

¹Department of Food and Nutrition, College of Life and Health Sciences, Hoseo University, Chungnam, Korea

,

Meiling Liu

¹Department of Food and Nutrition, College of Life and Health Sciences, Hoseo University, Chungnam, Korea

,

Ting Zhang

¹Department of Food and Nutrition, College of Life and Health Sciences, Hoseo University, Chungnam, Korea

› Author Affiliations

Abstract

Polycystic ovary syndrome (PCOS) is a highly prevalent disease in young women that also features increased insulin resistance. Genetic factors have a strong relationship with the etiology of PCOS. We assessed whether carrying THADA rs13429458 is associated with the development of PCOS by meta-analysis and whether the association is influenced by ethnicity. Articles were searched using PubMed, EMBASE, Cochrane Library, Korean scientific database, and Chinese and Indian medical databases to identify all eligible studies for evaluating the association of THADA rs13429458 and PCOS risk. The association was assessed in five genetic random effects models including the allelic (AG), recessive (RG), dominant (DG), homozygous (HMG), and heterozygous (HTG) genetic models. Subgroup analyses stratified by ethnicity (Asians and non-Asians) were assessed. Nine articles were selected and 1 association analysis of Korea PCOS study met Hardy–Weinberg equilibrium criteria. A set of 38 224 PCOS women and 120 173 healthy women were included. The AG and RG showed heterogeneity in the overall and Asian subjects, but the other genetic model did not exhibit heterogeneity in all subjects. AG, RG, DG, and HMG, but not HTG, exhibited publication bias in total subjects but there was no publication bias in all genetic models among Asians and non-Asians. The overall effect of THADA_rs13429458 on PCOS risk showed significant positive associations in pooling 10 studies. In sub-group analysis only Asians, but not non-Asians, had a positive association (AG: OR=1.24, p=0.001; RG: OR=1.32, p=0.002; DG: OR, 1.70, p<0.00001; HMG: OR, 1.71, p=0.002; HTG: OR=1.34, p=0,006). In conclusions, young Asian women with the minor allele (C) for THADA rs13429458 were at increased risk of PCOS.

Key words

polycystic ovary syndrome - THADA - rs13429458 - Asians - Caucasians

Full Text

References

References
1 Lizneva D, Suturina L, Walker W. et al. Criteria, prevalence, and phenotypes of polycystic ovary syndrome. Fertil Steril 2016; 106: 6-15
2 Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: Whatʼs new?. Adv Clin Exp Med 2017; 26: 359-367
3 Crespo RP, Bachega T, Mendonca BB. et al. An update of genetic basis of PCOS pathogenesis. Arch Endocrinol Metab 2018; 62: 352-361
4 Kakoly NS, Khomami MB, Joham AE. et al. Ethnicity, obesity and the prevalence of impaired glucose tolerance and type 2 diabetes in PCOS: A systematic review and meta-regression. Hum Reprod Update 2018; 24: 455-467
5 Bjonnes AC, Saxena R, Welt CK. Relationship between polycystic ovary syndrome and ancestry in European Americans. Fertil Steril 2016; 106: 1772-1777
6 Ha L, Shi Y, Zhao J. et al. Association study between polycystic ovarian syndrome and the susceptibility genes polymorphisms in Hui Chinese Women. PloS One 2015; 10: e0126505-e0126505
7 March WA, Moore VM, Willson KJ. et al. The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010; 25: 544-551
8 Louwers YV, Stolk L, Uitterlinden AG. et al. Cross-ethnic meta-analysis of genetic variants for polycystic ovary syndrome. J Clin Endocrinol Metab 2013; 98: E2006-E2012
9 Li T, Zhao H, Zhao X. et al. Identification of YAP1 as a novel susceptibility gene for polycystic ovary syndrome. J Med Genet 2012; 49: 254-257
10 Wang Z, Li T, Xing X. et al. Replication study of RAD54B and GREB1 polymorphisms and risk of PCOS in Han Chinese. Reprod Biomed Online 2013; 27: 316-321
11 Hayes MG, Urbanek M, Ehrmann DA. et al. Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 2015; 6: 7502
12 Day FR, Hinds DA, Tung JY. et al. Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun 2015; 6: 8464
13 Kowalczyk K, Franik G, Kowalczyk D. et al. Thyroid disorders in polycystic ovary syndrome. Eur Rev Med Pharmacol Sci 2017; 21: 346-360
14 Moraru A, Cakan-Akdogan G, Strassburger K. et al. THADA regulates the organismal balance between energy storage and heat production. Dev Cell 2017; 41: 72-81.e76
15 Christodoulou MI, Avgeris M, Kokkinopoulou I. et al. Blood-based analysis of type-2 diabetes mellitus susceptibility genes identifies specific transcript variants with deregulated expression and association with disease risk. Sci Rep 2019; 9: 1512
16 Brower MA, Jones MR, Rotter JI. et al. Further investigation in Europeans of susceptibility variants for polycystic ovary syndrome discovered in genome-wide association studies of Chinese individuals. J Clin Endocrinol Metab 2015; 100: E182-E186
17 Goodarzi MO, Jones MR, Li X. et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J Med Genet 2012; 49: 90-95
18 Little J, Higgins JP, Ioannidis JP. et al. STrengthening the REporting of Genetic Association Studies (STREGA)–an extension of the STROBE statement. Genet Epidemiol 2009; 33: 581-598
19 Higgins JPT, Thompson SG, Deeks JJ. et al. Measuring inconsistency in meta-analyses. BMJ: Brit Med J 2003; 327: 557
20 Chen Z-J, Zhao H, He L. et al. Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16. 3, 2p21 and 9q33. 3. Nat Genet 2011; 43: 55
21 Bao S, Ren Y-C, Chen Z-S. et al. THADA gene variants and polycystic ovary syndrome in a Hainan Chinese population. Int J Clin Exp Pathol 2016; 9: 11883-11889
22 Huang Y-H, Ding J-B, Li X. et al. Association of LHCGR gene, THADA gene, DENND1A gene single nucleotide polymorphism with polycystic ovary syndrome in Xinjiang. J Xinjiang Med Univ 2016; 39: 997-1003
23 Li X, Huang Y-H, Tian H-Q. et al. Association study between polycystic ovary syndrome and THADA gene polymorphisms in xinjiang uygur women. Reprod Develop Med 2017; 1: 80
24 Cui L-L. Analysis of phenotypes and their correlation with genotypes of susceptibility genes in PCOS. Shan Dong University 2013; 20-22
25 Lerchbaum E, Trummer O, Giuliani A. et al. Susceptibility loci for polycystic ovary syndrome on chromosome 2p16. 3, 2p21, and 9q33. 3 in a cohort of Caucasian women. Horm Metab Res 2011; 43: 743-747
26 Eriksen MB, Brusgaard K, Andersen M. et al. Association of polycystic ovary syndrome susceptibility single nucleotide polymorphism rs2479106 and PCOS in Caucasian patients with PCOS or hirsutism as referral diagnosis. Eur J Obstet Gynecol Reprod Biol 2012; 163: 39-42
27 Goodarzi MO, Jones MR, Li X. et al. Replication of association of DENND1A and THADA variants with polycystic ovary syndrome in European cohorts. J Med Genet 2012; 49: 90-95
28 Welt CK, Styrkarsdottir U, Ehrmann DA. et al. Variants in DENND1A are associated with polycystic ovary syndrome in women of European ancestry. J Clin Endocrinol Metab 2012; 97: E1342-E1347
29 Gilbert EW, Tay CT, Hiam DS. et al. Comorbidities and complications of polycystic ovary syndrome: An overview of systematic reviews. Clin Endocrinol (Oxf) 2018; 89: 683-699
30 Lim SS, Kakoly NS, Tan JWJ. et al. Metabolic syndrome in polycystic ovary syndrome: a systematic review, meta-analysis and meta-regression. Obes Rev 2019; 20: 339-352
31 Rosenfield RL, Ehrmann DA. The Pathogenesis of Polycystic Ovary Syndrome (PCOS): The Hypothesis of PCOS as Functional Ovarian Hyperandrogenism Revisited. Endocr Rev 2016; 37: 467-520
32 Azziz R, Carmina E, Chen Z. et al. Polycystic ovary syndrome. Nat Rev Dis Primers 2016; 2: 16057
33 Chatterjee N, Perrimon N. Thermogenesis by THADA. Dev Cell 2017; 41: 1-2
34 Glueck CJ, Goldenberg N. Characteristics of obesity in polycystic ovary syndrome: Etiology, treatment, and genetics. Metabolism 2019; 92: 108-120
35 Shi Y, Zhao H, Shi Y. et al. Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 2012; 44: 1020-1025
36 Voight BF, Scott LJ, Steinthorsdottir V. et al. Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Nat Genet 2010; 42: 579-589
37 Bednarska S, Siejka A. The pathogenesis and treatment of polycystic ovary syndrome: What's new ?. Adv Clin Exp Med 2017; 26: 359-367
38 Jin P, Xie Y. Treatment strategies for women with polycystic ovary syndrome. Gynecol Endocrinol 2018; 34: 272-277
39 Chan JC, Malik V, Jia W. et al. Diabetes in Asia: epidemiology, risk factors, and pathophysiology. JAMA 2009; 301: 2129-2140

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