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Objective: The aim of our study was to investigate whether breast cancer-related microRNA polymorphisms are associated with primary ovarian insufficiency (POI) risk., Methods: Four breast cancer-related microRNA polymorphisms (miR-27aA > G [rs895819], miR-135bC > T [rs74141216], miR-423C > A [rs6505162], and miR-608G > C [rs4919510]) were genotyped in 136 women with idiopathic POI and 224 controls of Korean ethnicity using polymerase chain reaction-restriction fragment length polymorphism analysis. Differences in genotype frequencies between cases and controls were compared. Odds ratios and 95% CIs were determined as measures of the strength of association between genotype and POI., Results: Two haplotypes (G-C-A-G and A-T-C-C) of miR-27a/miR-135b/miR-423/miR-608 were associated with increased POI risk. The haplotypes G-A-G of miR-27a/miR-423/miR-608 and A-T-C of miR-27a/miR-135b/miR-608 were associated with higher POI risk, whereas the G-T haplotype of miR-27a/miR-135b was associated with decreased POI risk. The association between POI risk and the G-A-G haplotype of miR-27a/miR-423/miR-608 remained significant after false discovery rate correction for multiple comparisons. The combined genotypes AA/CT/CC/CC, AG/CC/CA/GC, GG/CC/CC/CC, and GG/CC/CA/GG of miR-27a/miR-135b/miR-423/miR-608 were also associated with higher POI risk. Increased POI risk was observed in combined genotypes GG/CC/GG of miR-27a/miR-135b/miR-608; AA/CC/GC, AG/CA/GC, GG/CC/GG, GG/CC/CC, and GG/CA/GG of miR-27a/miR-423/miR-608; and GG/GG of miR-27a/miR-608; however, these associations were not significant after false discovery rate correction. None of the four microRNA polymorphisms alone was associated with POI risk., Conclusions: Our data suggest that breast cancer-related microRNA polymorphisms, including miR-27aA > G, miR-423C > A, and miR-608G > C, are associated with increased POI risk via interactions between miR-27aG, miR-423A, and miR-608G variants. However, our results should be interpreted cautiously because of our small sample size and the low statistical power of our study design.

Objective: The aim of this study was to investigate whether two polymorphisms in the promoter region of inhibin alpha (INHA) are associated with risk of idiopathic primary ovarian insufficiency (POI) in Korean women, which is a controversial topic., Study Design: We genotyped the INHA polymorphisms c.-16C>T (rs35118453) and c.-124A>G (rs11893842) of 136 POI patients and 225 controls in Korean women by polymerase chain reaction and restriction fragment length polymorphism analysis. We then compared differences in genotype and allele frequencies (AF) of the polymorphisms between the two groups to determine odds ratios (OR) and 95% confidence intervals (CI) as measures of the strength of association between genotype and POI., Results: There were no significant differences in genotype or AF of the polymorphisms between the POI patients and controls. Haplotype analysis revealed that the T-G haplotype of the two variant alleles was more frequent in POI patients than in the controls (OR=1.630, 95% CI=1.081-2.457). Combination genotype analysis showed that the CT+TT/GG genotype frequency was higher in POI patients than in the controls (OR=2.414, 95% CI=1.190-4.895)., Conclusions: We provide evidence to suggest that when the two variant alleles are combined, the c.-16C>T and c.-124A>G polymorphisms are associated with increased POI risk in Korean women. We postulate that interactions between the INHA polymorphisms may affect POI risk., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

We investigated whether microRNA (miRNA) polymorphisms (miR-146aC>G, miR-196a2T>C, and miR-499A>G) confer risk of premature ovarian failure (POF) in Korean women. DNA samples from 136 patients with POF and 234 controls were genotyped for the 3 miRNA single-nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism. The miR-146aCG/miR-196a2TC combined genotype was less frequent in patients than in controls (P < .05), conferring less susceptibility. Using haplotype-based multifactor dimensionality reduction analysis, the C-C-A and G-T-A inferred haplotypes (miR-146a/miR-196a2/miR-499) were less frequent in patients, suggesting protective effects (P < .05 for each), whereas the C-T-A and G-C-A haplotypes were more frequent in patients (P < .05 for each). The C-T and G-C haplotypes (miR-146a/miR-196a2) were more frequent in patients, whereas the C-C and G-T haplotypes were less frequent in patients (P < .05 for each). However, none of the 3 miRNA polymorphisms alone was associated with POF risk. Our findings suggest that putative gene-gene interaction between miR-146 and miR-196a2 may be involved in POF development.

Objective: The aim of our study was to investigate whether methylenetetrahydrofolate reductase (MTHFR) gene variant (MTHFR 677C>T) and thymidylate synthase (TS) gene variants (TS enhancer region [TSER] and TS 1494del6) confer a risk for premature ovarian failure (POF)., Methods: We genotyped 136 POF patients and 236 controls among Korean women for the three single nucleotide polymorphism sites using polymerase chain reaction restriction fragment length polymorphism analysis. Differences in the MTHFR 677C>T, TSER, and TS 1494del6 genotype frequencies between POF patients and controls were compared, and odds ratios (ORs) and 95% CIs were determined as a measure of the strength of the association between genotypes and POF., Results: The MTHFR 677CT and CT + TT variant genotypes were more frequent in POF patients than in controls (OR, 2.249; 95% CI, 1.317-3.843; and OR, 2.132; 95% CI, 1.268-3.585, respectively). The combined genotype frequencies of MTHFR 677CT + TT/TSER 3R3R and 677CT + TT/TS 1494del6 del6/del6 were higher in patients than in controls (OR, 2.300; 95% CI, 1.219-4.337; and OR, 3.314; 95% CI, 1.623-6.767, respectively). The T-3R-del6 and T-2R-del6 (MTHFR 677C>T/TSER/TS 1494del6) haplotypes were more frequent in patients (OR, 1.450; 95% CI, 1.050-2.002; and OR, 2.911; 95% CI, 1.191-7.117, respectively), whereas the C-2R-del6 haplotype was less frequent in patients (OR, 0.372; 95% CI, 0.152-0.912). The T-del6 (MTHFR 677/TS 1494del6) haplotype frequency was higher among patients (OR, 1.653; 95% CI, 1.206-2.266), whereas the C-del6 haplotype frequency was lower among patients (OR, 0.700; 95% CI, 0.516-0.950). We did not find an association between TSER or TS 1494del6 polymorphisms and POF., Conclusions: Our data suggest that the MTHFR 677T allele may increase the risk for POF, which could lead to the development of novel genetic markers for predicting the risk of POF in patients.

Objective: The aim of the study was to investigate whether the -604T>C, 1192G>A, and 1719A>T polymorphisms in the kinase insert domain-containing receptor (KDR) gene confer risk for premature ovarian failure (POF) in Korean women., Methods: DNA samples from 133 POF patients and 230 controls were genotyped for the three KDR single nucleotide polymorphisms by polymerase chain reaction-restriction fragment length polymorphism analysis., Results: The POF patients had significantly increased frequencies of the KDR -604TC and -604TC + CC genotypes (odds ratio [OR], 1.975; 95% CI, 1.219-3.201 and OR, 1.948; 95% CI, 1.221-3.109, respectively) and of the -604TC + CC/1192GG combined genotype (OR, 2.271; 95% CI, 1.359-3.795) and a decreased frequency of the 1192GA genotype (OR, 0.457; 95% CI, 0.231-0.905) compared with the controls. The genotype frequency of the 1719A>T polymorphism was not significantly different between the two groups. The frequencies of the KDR -604C/1192G/1719T, -604C/1192G, and -604C/1719T haplotypes (OR, 3.319; 95% CI, 1.564-7.041; OR, 2.083; 95% CI, 1.351-3.212; and OR, 1.979; 95% CI, 1.073-3.649, respectively) were significantly higher among POF patients than controls, whereas the -604T/1719T haplotype frequency (OR, 0.657; 95% CI, 0.472-0.915) was lower among POF patients., Conclusions: Carriers of the KDR -604C variant allele (-604TC and -604TC + CC genotypes; -604TC + CC/1192GG combined genotype; -604C/1192G/1719T haplotype, -604C/1192G haplotype, -604C/1719T haplotype) are consistently more prevalent among POF patients than among controls, suggesting that the KDR -604C allele may increase the risk of POF development in Korean women.

Objective: To study the association of vascular endothelial growth factor (VEGF) polymorphisms (-2578C>A, -1154G>A, -634G>C, and 936C>T) with premature ovarian failure (POF) in Korean patients., Study Design: Prospective case-control study. One hundred and thirty five patients with POF and confirmed serum follicle-stimulating hormone levels of >40IU/L before the age of 40 years and 120 healthy controls with at least one live birth, regular menstrual cycles, and karyotype 46, XX., Results: POF patients exhibited significantly different frequencies of the VEGF -1154GA genotype (odds ratio [OR], 2.002; 95% confidence interval [CI], 1.116-3.592; P=0.019), and -2578CA+AA/-1154GA+AA combination genotype (OR, 1.805; 95% CI, 1.013-3.217; P=0.044) compared to the control group. The frequency of the -2578A/-1154A haplotype (OR, 1.647; 95% CI, 1.017-2.677; P=0.041) was significantly higher in the POF group than in the control group., Conclusion: The VEGF -1154G>A mutation, -2578CA+AA/-1154GA+AA combination genotype, and -2578A/-1154A haplotype are significantly associated with POF in Korean women., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)