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


METHODS
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.


METHODS
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.
Department of Preventive Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan. uemura@basic.med.tokushima-u.ac.jp
Hirokazu
H
Uemura
Mineyoshi
M
Hiyoshi
Kokichi
K
Arisawa
Miwa
M
Yamaguchi
Mariko
M
Naito
Sayo
S
Kawai
Nobuyuki
N
Hamajima
Keitaro
K
Matsuo
Naoto
N
Taguchi
Naoyuki
N
Takashima
Sadao
S
Suzuki
Kazuyo
K
Hirasada
Haruo
H
Mikami
Keizo
K
Ohnaka
Aya
A
Yoshikawa
Michiaki
M
Kubo
Hideo
H
Tanaka
D000328:Adult; D000367:Age Factors; D000368:Aged; D000483:Alleles; D044466:Asian People; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007564:Japan; D008572:Menarche; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D047494:PPAR delta / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D014157:Transcription Factors / Q000235:genetics*
D006360:Heat-Shock Proteins; D047494:PPAR delta; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors