长寿蛋白 Klotho 基因多态性与老年男性患痴呆症的风险
Longevity Klotho gene polymorphism and the risk of dementia in older men.
作者信息
Almeida Osvaldo P, Morar Bharti, Hankey Graeme J, Yeap Bu B, Golledge Jonathan, Jablensky Assen, Flicker Leon
机构信息
School of Psychiatry & Clinical Neurosciences, University of Western Australia, Perth, Australia; WA Centre for Health & Ageing of Centre for Medical Research, Harry Perkins Institute of Medical Research, Perth, Australia; Department of Psychiatry, Royal Perth and Bentley Hospitals, Perth, Australia.
Centre for Clinical Research in Neuropsychiatry, School of Psychiatry and Clinical Neurosciences, University of Western Australia, MRF Building, 50 Murray Street, Perth 6000, Australia; Cooperative Research Centre for Mental Health, Carlton South, Victoria, Australia; Harry Perkins Institute of Medical Research and Centre for Medical Research, The University of Western Australia, 6 Verdun Street, Nedlands, WA 6009, Australia.
出版信息
Maturitas. 2017 Jul;101:1-5. doi: 10.1016/j.maturitas.2017.04.005. Epub 2017 Apr 8.
INTRODUCTION
Klotho variants (KL-VS) have been associated with increased longevity and better cognitive function. It is unclear whether they modulate dementia risk.
METHODS
We recruited 527 men aged 71-87 years who were free of cognitive impairment. We used data linkage to track the onset of dementia over 10 years. KL-VS genotyping (rs9536314 T/G) followed standard procedures.
RESULTS
The annual rate of dementia was 17.2‰ (95%CI=14.0-21.1; total=5053 person-years), and 14.0‰ (95%CI=10.6-18.4; 3582 person-years), 23.5‰ (95%CI=16.6-33.2; 1363 person-years) and 46.4‰ (95%CI=19.3-111.5; 108 person-years) for men with the TT, TG and GG genotypes. Compared with the TT genotype, the sub-hazard ratios of dementia associated with the TG and GG genotypes were 1.6 (95%CI=1.0, 2.5; p=0.030) and 3.5 (95%CI=1.3, 9.1; p=0.011).
DISCUSSION
The Klotho KL-VS variant is associated with an increase in the incidence of dementia in older men, in a dose-dependent fashion (intermediate for heterozygosis and highest for homozygosis).
引言
klotho基因变异体（KL-VS）与寿命延长和更好的认知功能相关。目前尚不清楚它们是否会调节痴呆风险。
方法
我们招募了527名年龄在71-87岁之间且无认知障碍的男性。我们通过数据关联追踪了10年内痴呆症的发病情况。KL-VS基因分型（rs9536314 T/G）遵循标准程序。
结果
痴呆症的年发病率为17.2‰（95%CI=14.0-21.1；总计5053人年），TT、TG和GG基因型男性的发病率分别为14.0‰（95%CI=10.6-18.4；3582人年）、23.5‰（95%CI=16.6-33.2；1363人年）和46.4‰（95%CI=19.3-111.5；108人年）。与TT基因型相比，与TG和GG基因型相关的痴呆症亚风险比分别为1.6（95%CI=1.0, 2.5；p=0.030）和3.5（95%CI=1.3, 9.1；p=0.011）。
讨论
klotho基因的KL-VS变异体与老年男性痴呆症发病率的增加相关，呈剂量依赖性（杂合子为中等风险，纯合子风险最高）。
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