Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population
Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population
复制标题
PPARD 和 PPARGC1A 的基因变异与日本普通人群的自然绝经时间相关
DOI：
10.1016/j.maturitas.2011.12.021
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发表时间：
2012
期刊：
影响因子：
4.9
通讯作者：
H
中科院分区：
文献类型：
--
作者：
Uemura;H.;Hiyoshi;M.;Arisawa;K.;Yamaguchi;M.;Naito;M.;Kawai;S.;Hamajima;N.;Matsuo;K.;Taguchi;N.;Takashima;N.;Suzuki;S.;Hirasada;K.;Mikami;H.;Ohnaka;K.;Yoshikawa;A.;Kubo M.;and Tanaka;H
绝经影响绝经后的健康风险。本研究旨在探讨过氧化物酶体增殖物激活受体（peroxisome proliferator-activated receptor，PPAR）相关基因的单核苷酸多态性（single nucleotide polymorphisms，SNPs）与冠心病的关系（PPARD，PPARG，和PPARGC 1A）和环境因素与日本普通人群自然绝经时间的关系。研究结果我们分析了1758名40岁至60岁女性的横断面数据，入组日本多机构协作队列（J-MICC）基线调查的69岁患者研究：主要结果测量自然绝经时间与其可能的协变量和靶基因变异的关系通过单变量和多变量考克斯比例风险模型进行评估。体重指数和初潮年龄晚与自然绝经早有显著相关。在PPARD中T-48444 C处具有次要等位基因的女性显示出较早自然绝经的显著更高的校正风险比1.57（95%置信区间：1.18-2.10）。相比之下，在PPARGC 1A中Thr 394 Thr处具有次要等位基因的女性显示出较早自然绝经的显著较低的校正风险比0.86（0.76-0.97）。这些协会没有实质性改变时，排除了自我报告的糖尿病史的受试者或年龄超过65 years. CONCLUSIONSPPARD和PPARGC 1A的基因变异可能与自然绝经的时间，可能是通过对卵巢的直接行动，在一般日本人群中重新分析。
OBJECTIVESTiming of menopause affects postmenopausal health risks. The objective of this study was to evaluate the associations of the single nucleotide polymorphisms (SNPs) in peroxisome proliferator-activated receptor (PPAR)-related genes (PPARD, PPARG, and PPARGC1A) and environmental factors with timing of natural menopause among the general Japanese population.STUDY DESIGNWe analyzed cross-sectional data from 1758 women aged 40–69 years who were enrolled in the baseline surveys of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.MAIN OUTCOME MEASURESAssociations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models.RESULTSLower body mass index and later age at menarche were significantly associated with earlier natural menopause. Women with minor alleles at T-48444C in PPARD showed a significantly higher adjusted hazard ratio of 1.57 (95% confidence interval: 1.18–2.10) for earlier natural menopause. In contrast, women with minor alleles at Thr394Thr in PPARGC1A showed a significantly lower adjusted hazard ratio of 0.86 (0.76–0.97) for earlier natural menopause. These associations did not substantially alter when re-analyzed after excluding the subjects who self-reported a history of diabetes or the subjects whose age was more than 65 years.CONCLUSIONSGene variants in PPARD and PPARGC1A might be associated with timing of natural menopause, probably through direct actions on the ovaries, among the general Japanese population.