Department of Surgery, Washington University in St Louis, St Louis, MO, USA.
Menopause. 2010 Jan-Feb;17(1):152-6. doi: 10.1097/gme.0b013e3181b63c68.
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.
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.
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.
The ALOX12 gene seems to be associated with the timing of natural menopause in white women.
自然绝经是女性生命中的一个重要生理事件。绝经时间影响许多绝经后全身疾病的风险，因此可能影响预期寿命。自然绝经年龄（ANM）在很大程度上是由遗传决定的，但候选基因的清单远未完成。本研究调查了 ALOX12 基因与 ANM 之间的可能关联。
在 210 名无关的白人女性随机样本中，对该基因的 6 个单核苷酸多态性（SNP）（rs9904779、rs2073438、rs11571340、rs434473、rs2307214 和 rs312462）进行了基因分型。然后分析了 SNP 和常见单倍型与 ANM 的关联。吸烟、饮酒和母乳喂养时间用作协变量。
两个 SNP，rs9904779 和 rs434473（编码蛋白质中天冬酰胺被丝氨酸取代）与 ANM 显著相关（分别为 P = 0.022 和 0.033）。两个 SNP 的次要等位基因似乎使绝经提前约 1.3-1.5 年，使绝经提前的风险增加 1.6 至 1.8 倍。所有 SNP 均表明与饮酒和母乳喂养时间存在显著或近乎显著的相互作用。五个常见单倍型也与 ANM 相关。
ALOX12 基因似乎与白人女性自然绝经的时间有关。
