| Backgrond:A previous genome-wide association studies (GWAS) in Chinese women with polycystic ovary syndrome (PCOS) identified RAB5B gene as a reproducible PCOS susceptibility locus. The RAB5B gene was also associated with glucose and insulin level.Objective:To determine the role of the RAB5B gene in the etiology of PCOS in(?) women of an independent sample in Cchinese Han population and its relationship with the clinical phenotype. Thus to discuss the genetis pathogenesis of PCOS.Methods:We found 17 single nucleotide polymorphisms (SNP) on RAB5B from 1000 Genomes database,3 of them (rs773114, rs 117894492, rs11171710) conformed to Hardy-Weinberg equilibrium after being analyzed through an online software (http://202.120.7.14/analysis/myAnalysis.php) (r2≥0.8). A total of 650 Chinese-Han women with PCOS and 893 healthy controls were recruited. The three SNPs were amplified by Ligase Detection Reaction-Polymerase Chain Reaction (LDR-PCR) to compare the allels and genotyps of the two groups.The body measurement parameters and endocrine metabolism index of all patients were measured. SPSS 19.0 softwares were employed for statistical analysis, P<0.05 was considered statistically significant.Results (1) The allele frequeneies of the three SNPs were described as below.:The A and G frequeneies of rs11171710 in RAB5B in PCOS were 47.0% and 53.0% while they were 42.7.3% and 57.3% respectively in control group。 The T and A frequeneies of rs773114 in RAB5B in PCOS were 32.0% and 68.0% while 27.4% and 72.6% in control group。 The A and G frequeneies of rs117894492 in RAB5B in PCOS were 10.6% and 89.4% while 10.1% and 89.9% in control group. The allele frequeneies of rs773114 in PCOS were significantly higher than that in control group(OR= 1.245, 95%CI=1.065-1.455, P= 0.006), and the difference remained significant after adjustment by permutation testing,(P= 0.016).The allele frequeneies of rs11171710 in PCOS were significantly higher than that in control group(OR= 1.192, 95%CI= 1.032-1.376, P= 0.017), and the difference remained significant after adjustment by permutation testing,(P= 0.045).While no significant differences were found in rs117894492 in PCOS and contro(P>0.05).(2)The genotype frequeneies of the three SNPs were followed. The genotype frequeneies of rs11171710 (AA/AG/GG) in RAB5B in PCOS were 23.4%,47.2% and 29.4, while they were 18.3%,48.8%,32.9% in control.The genotype frequeneies of rs773114 (TT/TA/AA) in RAB5B in PCOS were 10.3%,43.4% and 46.3.4% while they were 6.4%,42.1%,51.5% in control. The genotype frequeneies of rs117894492 (AA/AG/GG) in RAB5B in PCOS were 0.8%,19.7% and 79.5%, while they were 1.5%,17.4%,81.2% in control.The genotype frequencies of rs773114 in PCOS were significantly higher than that in control(P=0.009), and the difference remained significant after adjustment by permutation testing(P= 0.022).The genotype frequeneies of rsl 1171710 in PCOS were significantly higher than that in control(P= 0.038), but no significant difference were found after adjustment by permutation testing(P= 0.091), and no significant differences were found in rs117894492 beteen PCOS and control(P= 0.251, P= 0.491).(3)After adjustment for BMI, there is an obvious correlation of the effect allele Tof rs11171710 and A of rs773114 with PCOS (P<0.05)(4)The relationship of each locus of different genotypes with clinical indexes of metabolism were followed. In PCOS, the BMI, HOMA-IR, Fasting Glucose and 2h-Glucosein in TT genotypes of rs773114 were significantly higher than TA+AA genotypes (P<0.05)Conclusions rs773114 of RAB5B gene variant might be the susceptible gene for the PCOS in our study.The gene may play a role in the pathogenesis of PCOS by affecting the patient’s level of insulin and glucose regulation. |
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