ALOX12 gene is associated with the onset of natural menopause in white women.
OBJECTIVE
Natural menopause is a key physiological event in a woman's life. Timing of menopause affects risk for many postmenopausal systemic disorders and may thus influence life expectancy. Age at natural menopause (ANM) is largely determined genetically, but a list of candidate genes is far from complete. This study investigated the ALOX12 gene for its possible association with ANM.


METHODS
Six single-nucleotide polymorphisms (SNPs) of the gene (rs9904779, rs2073438, rs11571340, rs434473, rs2307214, and rs312462) were genotyped in a random sample of 210 unrelated white women. The SNPs and common haplotypes were then analyzed for their association with ANM. Smoking, alcohol consumption, and duration of breast-feeding were used as covariates.


RESULTS
Two SNPs, rs9904779 and rs434473 (encodes a replacement of asparagine by serine in the protein), were significantly associated with ANM (P = 0.022 and 0.033, respectively). The minor alleles of both SNPs seem to promote about 1.3- to 1.5-year earlier menopause and confer a 1.6 to 1.8 times higher risk for early menopause. All SNPs indicated significant or nearly significant interactions with alcohol use and duration of breast-feeding. Five common haplotypes were also associated with ANM.


CONCLUSIONS
The ALOX12 gene seems to be associated with the timing of natural menopause in white women.
Liu
Pengyuan
P
Department of Surgery, Washington University in St Louis, St Louis, MO, USA.
Lu
Yan
Y
Recker
Robert R
RR
Deng
Hong-Wen
HW
Dvornyk
Volodymyr
V
D000375:Aging / Q000235:genetics*; D001092:Arachidonate 12-Lipoxygenase / Q000235:genetics*; D005260:Female; D006801:Humans; D008593:Menopause / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People
D001092:Arachidonate 12-Lipoxygenase; C476558:ALOX12 protein, human