Meta-analysis On Relationship Between LHCGR, THADA, DENND1A Polymorphisms And Polycystic Ovary Syndrome

Objective:LHCGR, THADA, DENND1A has been reported to be associated with polycystic ovary syndrome susceptibility in Han Chinese by GWAS. However the results of all available studies are inconsistent or controversial. The objective of this study is to explore the association between LHCGR rs13405728, THADA rs12468394, rs13429458, rs12478601, DENND1A rs10818854, rs2479106, rs10986105 polymorphisms and polycystic ovary syndrome.Methods:The relevant studies were identified through a search of PubMed, Cochrane library, Excerpta Medica Database (Embase), Elsevier Science Direct and Chinese Biomedical Literature Database (CBM) until Jan 2016. The association between LHCGR, THADA, DENND1A polymorphisms and polycystic ovary syndrome risk was assessed by odds ratios (ORs) together with their 95% confidence intervals (CIs).Results:l.A total of 10 case-control studies were eventually identified.2.Seven studies are identified for LHCGR rs13405728 polymorphism with 7.220 cases and 2,6135 controls. LHCGR rs13405728 is significantly associated with polycystic ovary syndrome susceptibility in overall population (G versus A:OR= 0.73,95%CI 0.65-0.82, P= 0.000; GG+GA versus AA:OR= 0.73,95% CI 0.64-0.83, P= 0.000; GG versus AA+AG:OR= 0.58,95% CI 0.48-0.69, P= 0.000; GG vs AA: OR= 0.51,95% CI 0.43-0.62, P= 0.000; AG vs AA:OR= 0.75,95% CI 0.66-0.85, P= 0.000). In subgroup analysis, similar results were found in Asians, but results were opposite in Caucasians. 3.Eight studies were eventually identified for THADA, among which five studies with 8,040 cases and 2,7406 controls included for rsl2468394 polymorphism, seven studies including 8,310 cases and 27,411 controls available for rs13429458 polymorphism, and 3 studies containing 5,720 cases and 24,761 controls for rs12478601 polymorphism. We found a significant association between THADA rs12468394, rsl3429458 and rs12478601 polymorphisms and polycystic ovary syndrome susceptibility in overall population. In subgroup analysis, similar results were found in Asians, while in Caucasians only THADA rsl2468394 is associated with polycystic ovary syndrome,no significant association was detected between THADA rs13429458 and rsl2478601 polymorphism and polycystic ovary syndrome.4.Eight studies were eventually identified for DENND1A, among which four studies with 6.356 cases and 2,5461 contro1s included for rs10818854 polymorphism, eight studies including 8,550 cases and 27,806 controls available for rs2479106 polymorphism, and three studies containing 5,405 cases and 24,496 controls for rs 10986105 polymorphism. We found a significant association between DENND1A rs10818854, rs2479106 and rsl0986105 polymorphisms and polycystic ovary syndrome susceptibility in overall population. In subgroup analysis, similar results were found in Asians, while in Caucasians no significant association was detected between rs2479106 and polycystic ovary syndrome.Conclusions:The present meta-analysis suggests that LHCGR rs13405728, THADA rs12468394, rs12478601, DENND1A rs10818854, rs2479106, rs10986105 polymorphisms may be assiciated with polycystic ovary syndrome susceptibility, but there are ethic differences. All these seven polymorphisms are risk factors for Asians with polycystic ovary syndrome, while in Caucasians LHCGR rs13405728, THADA rs13429458, rs12478601. DENND1A rs2479106 are not related to polycystic ovary syndrome susceptibility. Further large and well-designed studies are needed to confirm this association.