title: 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, 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.
authors.affiliation: Department of Epidemiology (XM), College of Preventive Medicine, Third Military Medical University, Chongqing; Department of Cardiology (YC, XZ, JC, SY), Affiliated Yixing People's Hospital of Jiangsu University, People's Hospital of Yixing City, Yixing; and Department of Epidemiology and Biostatistics (CS), School of Public Health, Nanjing Medical University, Nanjing, China.
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Ma
authors.forename: Yanchun
authors.initials: Y
authors.lastname: Chen
authors.forename: Xianghai
authors.initials: X
authors.lastname: Zhao
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Chen
authors.forename: Chong
authors.initials: C
authors.lastname: Shen
authors.forename: Song
authors.initials: S
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008594:Menopause, Premature / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D016649:Primary Ovarian Insufficiency / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012307:Risk Factors
chemical_list: C571457:MIRN518 microRNA, human; D035683:MicroRNAs; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II