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首页> 外文期刊>The journals of gerontology.Series A. Biological sciences and medical sciences >The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects
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The Longevity-Associated SH2B3 (LNK) Genetic Variant: Selected Aging Phenotypes in 379,758 Subjects

机译：寿命相关的SH2B3（LNK）遗传变体：379,758个受试者中的选定老化表型

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摘要

Human SH2B3 is involved in growth factor and inflammation signaling. A SH2B3 missense variant (rs3184504) is associated with cardiovascular diseases plus breast, colorectal, and lung cancers, with highly correlated variants across the ATXN2/SH2B3/BRAP locus linked to parental age at death, suggesting a geroscience common mechanism of aging and disease. To better understand the SH2B3-related aging pathway and its potential as an intervention target, we undertook a phenotype-wide association study (PheWAS) of 52 aging traits. Data were obtained from 379,758 European-descent UK Biobank participants, aged 40-70 at baseline: 27% of participants were CC homozygotes and 23% TT at rs3184504. Parental extreme longevity (mothers aged =98 years, fathers aged >= 96 years) was more common in CC versus TT (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.07 to 1.29) with an additive per allele effect. The C allele associated with better cognitive function and white blood cell counts were more likely to be normal. The C allele reduced risks of coronary heart disease (OR = 0.95, 95% CI: 0.93 to 0.96) but was also associated with a modestly higher cancer rate (OR = 1.03, 95% CI: 1.02 to 1.04), suggesting a trade-off across aging outcomes and limiting its potential as an anti-aging target.
机译：人SH2B3参与生长因子和炎症信号传导。SH2B3错义变异体（rs3184504）与心血管疾病以及乳腺癌、结直肠癌和肺癌相关，ATXN2/SH2B3/BRAP基因座上的高度相关变异体与父母的死亡年龄相关，表明衰老和疾病的共同机制是老龄化。为了更好地了解SH2B3相关衰老途径及其作为干预目标的潜力，我们对52种衰老特征进行了表型广泛关联研究（PHEWS）。数据来自379758名欧洲裔英国生物库参与者，基线年龄40-70岁：27%的参与者为CC纯合子，23%的参与者为TT，rs3184504。父母极端长寿（母亲年龄=98岁，父亲年龄>=96岁）在CC和TT（优势比[OR]=1.18，95%置信区间[CI]：1.07到1.29）中更常见，具有加性等位基因效应。与更好的认知功能和白细胞计数相关的C等位基因更可能是正常的。C等位基因降低了冠心病的风险（OR=0.95，95%CI:0.93至0.96），但也与略高的癌症发病率相关（OR=1.03，95%CI:1.02至1.04），这表明在衰老结果之间存在权衡，并限制了其作为抗衰老靶点的潜力。

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