arntl (bmal1) and npas2 gene variants contribute to fertility and seasonalityarntl(bmal1)和npas2基因变异导致生育和季节性.pdfVIP

ARNTL (BMAL1) and NPAS2 Gene Variants Contribute to Fertility and Seasonality 1,2 2 3 ¨ 1,4 1 Leena Kovanen , Sirkku T. Saarikoski , Arpo Aromaa , Jouko Lonnqvist , Timo Partonen * 1 Department of Mental Health and Substance Abuse Services, National Institute for Health and Welfare, Helsinki, Finland, 2 Department of Alcohol, Drugs and Addiction, National Institute for Health and Welfare, Helsinki, Finland, 3 Division of Welfare and Health Policies, National Institute for Health and Welfare, Helsinki, Finland, 4 Department of Psychiatry, University of Helsinki, Helsinki, Finland Abstract Background: Circadian clocks guide the metabolic, cell-division, sleep-wake, circadian and seasonal cycles. Abnormalities in these clocks may be a health hazard. Circadian clock gene polymorphisms have been linked to sleep, mood and metabolic disorders. Our study aimed to examine polymorphisms in four key circadian clock genes in relation to seasonal variation, reproduction and well-being in a sample that was representative of the general population, aged 30 and over, living in Finland. Methodology/Principal Findings: Single-nucleotide polymorphisms in the ARNTL, ARNTL2, CLOCK and NPAS2 genes were genotyped in 511 individuals. 19 variants were analyzed in relation to 31 phenotypes that were assessed in a health interview and examination study. With respect to reproduction, women with ARNTL rs2278749 TT genotype had more miscarriages and pregnancies, while NPAS2 rT carriers had fewer miscarriages. NPAS2 rs2305160 A allele carriers had lower Global Seasonality Scores, a sum score of six items i.e. seasonal variation of sleep length, so