Gene variants in PPARD and PPARGC1A are associated with timing of natural menopause in the general Japanese population

详细信息	查看全文 | 推荐本文 |

• 作者：Hirokazu Uemura^a ; ¹ ; ^{uemura@basic.med.tokushima-u.ac.jp} ; Mineyoshi Hiyoshi^a ; ¹ ; Kokichi Arisawa^a ; ¹ ; Miwa Yamaguchi^a ; ¹ ; Mariko Naito^b ; ¹ ; Sayo Kawai^b ; ¹ ; Nobuyuki Hamajima^b ; ¹ ; Keitaro Matsuo^c ; ¹ ; Naoto Taguchi^d ; ¹ ; Naoyuki Takashima^e ; ^f ; ¹ ; Sadao Suzuki^g ; ¹ ; Kazuyo Hirasada^h ; ¹ ; Haruo Mikamiⁱ ; ¹ ; Keizo Ohnaka^j ; ¹ ; Aya Yoshikawa^k ; ¹ ; Michiaki Kubo^l ; ¹ ; Hideo Tanaka^c ; ¹
• 关键词：SNPs ; single nucleotide polymorphisms ; PPAR ; peroxisome proliferator-activated receptor ; J-MICC Study ; Japan Multi-institutional Collaborative Cohort Study ; PGC-1伪 ; PPAR纬 coactivator 1-alpha ; POF ; premature ovarian failure ; HWE ; Hardy&ndash ; Weinberg equ
• 刊名：Maturitas
• 出版年：2012
• 期刊代码：192_03785122
• 类别：med
• 出版时间：April, 2012
• 卷：71
• 期：4
• 页码：369-375
• 文件大小：307 K

摘要

Objectives

Timing 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 design

We 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 measures

Associations of timing of natural menopause with its probable covariates and with target gene variants were evaluated by univariate and multivariate Cox proportional hazards models.

Results

Lower 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.

Conclusions

Gene 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.