| ObjectiveThe study is to evaluate whether genetic polymorphisms of Nuclear factorerythroid2-related factor2(Nrf2) gene are associated with the polycystic ovarysyndrome (PCOS) in Guangdong district population.MethodsWe genotyped three SNPs,617G>/T (rs6721961),651C>T (rs6706649) and653T> C (rs35652124), in the Nrf2promoter region in199PCOS patients and138controls. Polymorphisms of this gene are detected by using the polymerase chainreaction technology. Genotypic frequencies, allelic frequencies and haplotypes werecompared between patients and controls, and these results were analyzed in respect toclinical test datas.Results1. The prevalence rates of rs6721961polymorphism site genotypes G/G, T/T andG/T were60.80%,5.53%,33.67%in PCOS and58.70%，7.25%，34.06%incontrol group，respectively．Those of SNP rs6706649genotypes C/C and C/Twere87.94%,12.06%in PCOS,and89.13%,10.87%in control group.Genotype C/C,TT,C/T of the SNP rs35652124’s prevalence rates were25.56%,22.26%,51.76%in PCOS,and23.19%,27.54%,49.83%in control group.No significant differences were observed in the genotypes distributions of these three SNPs loci between the PCOS and control group（P>0.05）.2. In this experiment, the frequencies of rs6721961G and T alleles were77.64%，75.57%in PCOS group and22.36%，24.43%in control group,respectively．SNPrs6706649C and T alleles’ frequencies were93.72%,94.57%in PCOS group,and6.28%,5.43%in control group．Those of SNP rs35652124C and T were51.51%,47.83%in PCOS group,and48.49%,52.17%in control group．Nosignificant differences were observed between the PCOS cases and control groupsin allele frequencies of these three SNPs(rs6721961χ2=0.34，P>0.05, rs6706649χ2=0.21，P>0.05,rs35652124χ2=0.34，P>0.05）.3. From haploid type analysis,3kinds of haploid type (GCT, GCC, TCT of Nrf2promoters,without the GTT) were identified according to these three SNPs loci.The prevalence rate of haplotypes GCT, GCC, TCT were4.02%,25.13%,5.03%in PCOS and5.07%,21.19%,6.52%in control group，respectively．All thesehaplotypes’ comparisons were found no significant difference (P>0.05）betweenPCOS patients and controls.4. The individuals of the PCOS cohort were further divided into subgroups, basedon body mass index (BMI), obese PCOS (BMI≥25) cases and non-obese PCOS(BMI<25). In PCOS cohort,52women in total were obese and35showedcentral obesity (WHR≥0.8).The numbers of obesity occurred in the genotypesGG,TT,TG of SNP rs6721961were26,7,19in the obese subgroup (n=52), and95,5,47in non-obese subgroup (n=147),respectively. Observation proved thatthere is a significant difference (χ2=8.04，P<0.05) in rs6721961locus genotypesbetween the obese and the non-obese patients. But between the central obese andthe non-central obese patients, there was no differences in these three genotypes（χ2=0.52，P>0.05）. We found differences in genotypes CC、CT of SNPrs6706649and CC,TT,TC of SNP rs35652124,neither between the obese andnon-obese patients (rs6706649χ2=0.56,P>0.05, rs35652124χ2=2.701，P>0.05）nor between the central obese and non-central obese patient（srs6706649χ2=1.29，P>0.05,rs35652124χ2=2.29，P>0.05）. 5. We clarified85cases with insulin resistance（HOMA-IR≥1.66）in the PCOSpatients to be the IR group. No significant differences were observed in thegenotypes distributions of SNP rs6721961,rs6706649,rs35652124between theIR group and no IR group（rs6721961χ2=3.17，P>0.05，s6706649χ2=0.54，P>0.05，rs35652124χ2=3.63，P>0.05）.Further analysis was executed to analyzethe genotypes distributions of SNP rs6721961, rs6706649, rs35652124betweenthe obese and non-obese patients in the IR cohort. Finally, there was also nosignificant differences between the subgroups in the IR cohort.（rs6721961χ2=0.02, P>0.05; rs6706649χ2=0.00，P>0.05; rs35652124χ2=1.83,P>0.05）.6. Experimental results of the serum TC, TG, HDL, LDL, Lpa, apoE, apoA1, apoBlevels, showed that there were no significant differences between the SNPrs6721961genotypes in the PCOS group, as well as the SNP rs6706649andrs35652124（P>0.05）.We defined abnormal lipid metabolism according to the2007Chinese Adult Dyslipidemia Prevention Guide, includinghypertriglyceridemia, high cholesterol, high high-density lipoprotein and highlow-density lipoprotein. Comparing to the normal plasma lipids subjects, therewere no significant differences between SNP rs6721961genotypes distributionsin all abnormal lipid metabolism PCOS groups (P>0.05), as well as the SNPsrs6706649and (P>0.05).The same results were certified in rs6706649CC, CTand rs35652124CC, TT and TC genotype (P>0.05).Conclusions1. Our datas may not support an association between functional polymorphismsrs6721961, rs6706649, rs35652124of Nrf2and pathogenesis of PCOS.2. Our results suggest that the SNP rs6721961, in the promoter region of the Nrf2gene contributes to the PCOS obesity phenotype, but not to the type of the obesityin Guangdong population. However, other two SNPs, rs6706649andrs35652124,may have no association with PCOS obesity phenotype or the typeof obesity.3. This study may demonstrates no significant association between three SNPs, rs6721961, rs6706649, rs35652124, in Nrf2gene with the IR or abnormal lipidmetabolism of PCOS in Guangdong crowd. |
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