The Association Between Snps Related To Chinese Women With Pof And Patients In Serbian

Background and Objective:Premature ovarian failure (POF) is defined as ovarian function failure of the women before40years. It affects approximately1%of women under40years and0.1%of women under30years. The causes and mechanisms of POF are complicated. Most of the cases are definitively defined as "idiopathic premature ovarian failure".In recent years, a series of candidate genes related to oogenesis has been reported to be candidates for POF. However, only a small part of patients can be explained by dysfunction of these genes. Previous genome-wide association study (GWAS) was performed in an initial discovery set of391well-documented Chinese Han POF patients and verified in400patients accordingly. Eight related single-nucleotide polymorphisms (SNPs)(rs10464815,rs10808365、rs3847152、 rs3847153、rs3847154、rs3843552、rs10955242、rs3843555) were found at8q22.3. Tough no specific candidate genes were found in the immediate region of8q22.3, the authors speculated the existence of a long-distance regulatory region that had relevance to the control of ovarian differentiation or oogenesis. Another association study of early menopause (EM) was performed in371unrelated Chinese Han POF patients. Three significant SNPs (rs2278493in HK3, rs2234693in ESR1and rs12611091in BRSK1) were found. By now, there are no further validation studies reported in other races. Based on the principle of minor allele frequency (MAF)>3%,SNPs rs2278493, rs2234693, rsl2611091, rs3847153and rs3108910were selected to confirm their correlations with POF in Serbian, and the allele frequency of different SNPs between Serbian POF and Chinese Han POF populations will be compared as well.Material and methods:According to the criteria of POF, a total of197Serbian women with idiopathic POF and552normal Serbian women as controls were selected in the United Kingdom. They were kinship among the patients. The peripheral whole-blood was collected for each subject, and then genomic DNA was isolated. The five SNPs (rs2278493of HK3gene, rs2234693of ESR1gene, rs12611091of BRSK1gene, rs3847153and rs3108910of8q22.3) were amplified by polymerase chain reaction (PCR) and then directly sequenced to screen variants. Statistical analysis of allele frequencies between cases and controls was compared using χ2test. The analysis was performed using the Statistical Package for the Social Sciences software (SPSS19.0) and a P<0.05were accepted statistically significant.Results:(1) Loci selected for association analysis in POF and controls in Serbian population:A allele frequency, which located at rs2278493(A/G polymorphism) of HK3gene are not statistically significant (31.2%vs.30.5%, respectively, P=0.798>0.05); C allele frequency, which located at rs2234693(C/T polymorphism) of ESR1gene are not statistically significant (46.1%vs.49.3%, respectively, P=0.296>0.05); C allele frequency, which located at rs12611091(C/T polymorphism) of BRSK1gene are not statistically significant (54.3%vs.52.9%, respectively, P=0.629>0.05);C allele frequency, which located at rs3847153(C/T polymorphism) on8q22.3are not statistically significant (4.3%vs.4.6%, respectively, P=0.803>0.05);G allele frequency, which located at rs3108910(G/A polymorphism) on8q22.3are not statistically significant (26.1%vs.23.7%, respectively, P=0.339>0.05).(2) Allele frequency of SNPs between Serbian POF patients and China han POF patient:A allele frequency, which located at rs2278493(A/G polymorphism) of HK3gene are not statistically significant (31.2%vs.34.51%, respectively, P=0.264>0.05);C allele frequency, which located at rs2234693(C/T polymorphism) of ESR1gene are statistically significant (46.1%vs.36.55%, respectively, P=0.002<0.05);C allele frequency, which located at rs12611091(C/T polymorphism) of BRSK1gene are statistically significant (54.3%vs.75.78%, respectively, P<0.0001); C allele frequency, which located at rs3847153(C/T polymorphism) on8q22.3are statistically significant (4.3%vs.30.08%, respectively, P<0.0001); G allele frequency, which located at rs3108910(G/A polymorphism) on8q22.3are statistically significant (26.1%vs.52.05%, respectively, P<0.0001).Conclusion:The result of present study showed that the SNPs (rs2278493in HK3gene, rs2234693in ESR1gene, rs12611091in BRSK1gene, rs3847153and rs3108910in8q22.3region) were not significantly associated with Serbian women with POF. And the differences of allele frequency with these SNPs between Serbian and Chinese Han POF patients showed statistically significantly, which suggested that the high genetic heterogeneity between different races with POF.