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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
Xiangyu Ma, Yanchun Chen, Xianghai Zhao, Jinfeng Chen, Chong Shen, Song Yang

Published: 01 October 2014 by Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins in Medicine
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins, Volume 93; 10.1097/md.0000000000000093
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, 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 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 (β = 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.
Keywords: genetic polymorphisms, breast cancer, Dyslipidemia, Tgfbr2, han, ANM, Natural Menopause, Chinese women

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