Arking Dan E, Fallin Daniele M, Fried Linda P, Li Tao, Beamer Brock A, Xue Qian Li, Chakravarti Aravinda, Walston Jeremy
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, 733 N. Broadway, Baltimore, MD 21205, USA.
J Am Geriatr Soc. 2006 May;54(5):823-6. doi: 10.1111/j.1532-5415.2006.00693.x.
To determine whether genetic variants in the ciliary neurotrophic factor (CNTF) gene are associated with muscle strength in older women.
Cross-sectional analysis of baseline data from the Women's Health and Aging Studies I (1992) and II (1994), complementary population-based studies.
Twelve contiguous ZIP code areas in Baltimore, Maryland.
Three hundred sixty-three Caucasian, community-dwelling women aged 70 to 79.
Participants were genotyped at the CNTF locus for eight single nucleotide polymorphisms (SNPs), including the null allele rs1800169. The dependent variables were grip strength and the frailty syndrome, identified as presence of three or more of five frailty indicators (weakness, slowness, weight loss, low physical activity, exhaustion). In addition to genotypes, independent variables of body mass index (BMI) and osteoarthritis of the hands were included.
Using multivariate linear regression, single SNP analysis identified five SNPs significantly associated with grip strength (P<.05), after adjusting for age, BMI, and osteoarthritis. Haplotype analysis was performed, and a single haplotype associated with grip strength was identified (P<.01). The rs1800169 null allele fully explained the association between this haplotype and grip strength under a recessive model, with individuals homozygous for the null allele exhibiting a 3.80-kg lower (95% confidence interval=1.01-6.58) grip strength. No association was seen between the CNTF null allele and frailty.
Individuals homozygous for the CNTF null allele had significantly lower grip strength but did not exhibit overt frailty. Larger prospective studies are needed to confirm this finding and extend it to additional populations.
确定睫状神经营养因子（CNTF）基因的遗传变异是否与老年女性的肌肉力量相关。
对妇女健康与衰老研究I（1992年）和II（1994年）的基线数据进行横断面分析，这两项研究是基于人群的补充研究。
马里兰州巴尔的摩的12个相邻邮政编码区域。
363名年龄在70至79岁之间的白人社区居住女性。
对参与者的CNTF基因座进行基因分型，检测8个单核苷酸多态性（SNP），包括无效等位基因rs1800169。因变量为握力和衰弱综合征，衰弱综合征定义为存在五项衰弱指标（虚弱、行动迟缓、体重减轻、体力活动少、疲惫）中的三项或更多项。除了基因型外，还纳入了体重指数（BMI）和手部骨关节炎等自变量。
使用多变量线性回归，单SNP分析在调整年龄、BMI和骨关节炎后，确定了5个与握力显著相关的SNP（P<0.05）。进行了单倍型分析，确定了一个与握力相关的单倍型（P<0.01）。在隐性模型下，rs1800169无效等位基因完全解释了该单倍型与握力之间的关联，无效等位基因纯合个体的握力低3.80千克（95%置信区间=1.01-6.58）。未发现CNTF无效等位基因与衰弱之间存在关联。
CNTF无效等位基因纯合个体的握力显著较低，但未表现出明显的衰弱。需要进行更大规模的数据研究来证实这一发现并将其扩展到其他人群。
