Association Study Of AQP8in Women With Polycystic Ovary Syndrome

BACKGROUND:Polycystic ovary syndrome (PCOS), which affects approximately6%to8%of women of reproductive age, represents one of the most common endocrine disorders in female worldwide. Chronic anovulation in this syndrome affects the female reproductive health and is associated with certain long-term metabolic complications. It has been identified that one mechanism responsible for PCOS is an intrinsic abnormality of follicle development in the ovary as the existence and proliferation of granulosa cells (GCs) are altered in patients with PCOS. Aquaporins (AQPs) are water-transforming channel proteins which are expressed in cell membranes of various organs. As the role of these water channel proteins is of paramount importance in a myriad of physiologic processes in human beings, it is conceivably expected that alterations in AQP genes or deficiency in AQPs may lead to morbid states. With respect to the mediation function, the presence of AQPs in GCs suggests that water permeability of antral follicles occurs primarily through transcellular mechanisms. This mechanism might be important in folliculogenesis. Moreover, overexpression of AQPs has been found to be related to enhanced apoptotic rate of GCs. By the investigation of the role of AQP8in female reproductive function in a knockout mouse model, Su et al. drew a conclusion that AQP8is the major water channel in granulose cell. In addition, they reported that AQP8deletion significantly decreased granulose cell water permeability and protected granulose cells from apoptosis, which may be responsible for the increased fertility in AQP8knockout female mice. These findings suppose that AQP8gene might affect female reproductive physiology. In this regard, the present research was designed to investigate the association between AQP8and PCOS.OBJECTIVE:The aim of the present study was to elucidate whether AQP8gene polymorphisms are associated with the development of PCOS.METHODS:We enrolled192Northern Han Chinese women with PCOS and191control women from the same ethnical group. Six tagSNPs of AQP8were selected (i.e., rs7198838, rs1076973, rs1076974, rs2287797, rs2287798, and rs2287796) from the HapMap Chineses database (phase Ⅱ, released22). High resolution melting (HRM) was used to genotype4of the6SNPs of AQP8(AA, AG, GG in rs7198838; AA, AG in rs1076973; AA, AG, GG in rs1076974; GG, GT, TT in rs2287796). Because HRM failed to distinguish the genotypes of the remaining2SNPs (rs2287798and rs2287797), direct sequencing was applied.RESULTS:By comparing the allelic frequencies, we found that the frequency of risk allele G of rs2287798was significantly higher in the PCOS group (P=7.0E-4, OR=1.642,95%CI:1.233-2.187). For the genotype-phenotype correlation analysis, Allele frequencies of the HA, OA and PCO groups were significantly different from the controls (P=0.011,0.001,0.001, respectively). Frequency of G allele was significant higher in both classical and additional PCOS patients than in controls (P=0.018,0.003). However, no significant difference was found in the clinical data analysisCONCLUSION:Our results suggest that AQP8gene might be a novel candidate forthe pathogenesis of PCOS.