ALOX12 基因与白人女性自然绝经的发生有关。
ALOX12 gene is associated with the onset of natural menopause in white women.
机构信息
Department of Surgery, Washington University in St Louis, St Louis, MO, USA.
出版信息
Menopause. 2010 Jan-Feb;17(1):152-6. doi: 10.1097/gme.0b013e3181b63c68.
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.
目的
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。
方法
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。
结果
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。
结论
ALOX12 基因似乎与白人女性自然绝经的时间有关。
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