Dataset Information

Association study of TGFBR2 and miR-518 gene polymorphisms with age at natural menopause, premature ovarian failure, and early menopause among Chinese Han women.

ABSTRACT: Age at natural menopause (ANM), a highly heritable phenotype, has been identified to be closely associated with major hormone-related diseases, including breast cancer and gynecological cancers. We previously identified an important role for the transforming growth factor, ? receptor II (TGFBR2) gene polymorphisms in breast cancer susceptibility among Asian women. Considering the important role of ANM in breast carcinogenesis, we hypothesized that TGFBR2 signals were involved in the formation of natural menopause.In a population-based study of 1844 Chinese women, we evaluated the effect of the genetic polymorphisms of TGFBR2 and miR-518 to determine if they are associated with ANM, premature ovarian failure (POF), and early menopause (EM) risk.No significant differences in the distribution of body mass index, education levels, smoking, drinking, and hypertension were detected between POF and EM cases and controls except for POF cases that were older (P?=?0.015) than controls and more likely to have dyslipidemia (P?=?0.002). The results showed that miR-518 rs7256241 was significantly associated with ANM. The carriers of minor allele G of rs7256241 have significantly higher ANM than those of the major allele homozygotes TT (??=?0.385, P?=?0.035). TGFBR2 rs3773661 was significantly associated with POF, with odds ratio (OR) (95% confidence intervals [CIs]) of 0.66 (0.47-0.94) associated with per minor allele C (P?=?0.023). The quartiles of genetic risk score were significantly associated with POF (OR, 1.27; 95% CI, 1.02-1.58; Ptrend?=?0.034). Sensitivity analyses confirmed the robustness of these findings and no significant interactions were detected.This study provides evidence to implicate TGFBR2 and miR-518 gene polymorphisms as novel susceptibility factors for ANM, POF, and EM in Asians. Further research on these genetic regions will enhance our understanding of the genetic basis of natural menopause.

SUBMITTER: Ma X

PROVIDER: S-EPMC4616299 | biostudies-other | 2014 Oct

REPOSITORIES: biostudies-other

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Association study of TGFBR2 and miR-518 gene polymorphisms with age at natural menopause, premature ovarian failure, and early menopause among Chinese Han women.

Ma Xiangyu X Chen Yanchun Y Zhao Xianghai X Chen Jinfeng J Shen Chong C Yang Song S

Medicine 20141001 20

Age at natural menopause (ANM), a highly heritable phenotype, has been identified to be closely associated with major hormone-related diseases, including breast cancer and gynecological cancers. We previously identified an important role for the transforming growth factor, β receptor II (TGFBR2) gene polymorphisms in breast cancer susceptibility among Asian women. Considering the important role of ANM in breast carcinogenesis, we hypothesized that TGFBR2 signals were involved in the formation of ...[more]

PMID: 25365407

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Project description:Premature ovarian failure (POF) is an ovarian defect characterized by the premature depletion of ovarian follicles in individuals <40 years old, and is a major cause of infertility in females. Genetic factors are considered to be responsible for the development of POF, however, the exact pathogenesis remains to be elucidated in the majority of cases. In the present study, the single nucleotide polymorphisms (SNPs) of growth differentiation factor 9 (GDF9), bone morphogenetic protein 15 (BMP15), inhibin ?B (INHBB) and follicle stimulating hormone receptor (FSHR) genes were investigated, and their association with POF in a Chinese Hui population of the Ningxia Hui Autonomous Region in western China was evaluated. Peripheral blood samples were collected from 63 patients diagnosed with POF (POF group) and 58 normal control individuals (control group), from which the genomic DNA was isolated. The GDF9, BMP15, INHBB and FSHR genes were amplified using polymerase chain reaction assays, and their SNPs were determined by sequencing. In the four SNPs identified across the GDF9 loci, D57Y (169G>T), rs1049127 (546G>A), rs254286 (447C>T) and rs254285 (969C>G), the frequencies of the 546G>A genotype and allele A were significantly higher in the POF group, compared with the normal control group (34.92, vs. 6.90%; P<0.05 and 19.05, vs. 3.23%; P<0.05, respectively), while no significant differences were observed in the occurrence of the c.447C>T and c.969C>G mutations between the two groups (60.32, vs. 50% and 50.79, vs. 55.17%, respectively). The c.169G>T mutation within the GDF9 gene was only detected in two patients with POF, and the mutation did not occur in the normal control group. A total of three SNPs were detected within the BMP15 gene, including rs3810682 (-9C>G), rs79377927 (788_789insTCT) and rs17003221 (852C>T), and no significant differences were observed in the frequencies of the -9C>G and 852C>T genotypes between the POF and control groups (7.94, vs. 6.90% and 4.76, vs. 3.45%, respectively). The 788_789insTCT genotype was detected in only two patients with POF. A novel mutation, c.1095C>A, was identified in exon 2 of the INHBB gene, however, no significant difference was found in the occurrence of the mutation between the two groups (30.16, vs. 22.41%; P>0.05). The rs6165 (919G>A) and rs6166 (2039G>A) SNPs were detected in exon 10 of the FSHR gene; however, no significant difference was observed in the genotype frequencies between the two groups (92.06, vs. 91.38% and 96.83, vs. 93.10%, respectively). These results demonstrated that GDF9 c.169G>T (D57Y), c.546G>A (rs1049127), and BMP15 rs79377927 (788_789insTCT) were associated with POF in the Chinese Hui population.

Dataset Information

Association study of TGFBR2 and miR-518 gene polymorphisms with age at natural menopause, premature ovarian failure, and early menopause among Chinese Han women.

Publications

Association study of TGFBR2 and miR-518 gene polymorphisms with age at natural menopause, premature ovarian failure, and early menopause among Chinese Han women.

Similar Datasets

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