De Luca Maria, Crocco Paolina, De Rango Francesco, Passarino Giuseppe, Rose Giuseppina
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Department of Biology, Ecology and Earth Science, University of Calabria, Rende 87036, Italy.
Mech Ageing Dev. 2016 Apr;155:55-9. doi: 10.1016/j.mad.2016.03.003. Epub 2016 Mar 9.
Studies in animal models and humans suggest that reduced growth and adult stature are associated with lifespan extension. Moreover, epidemiological studies reported a positive association between adult height and risk of multiple cancers. Yet, it is unclear which factors mediate these relationships. Laminins are major components of the basement membranes and cooperate with growth factors and matrix-dependent receptors in cell proliferation and differentiation. Previously, we reported the association of rs659822-C/T in LAMA5, encoding the laminin-α5 chain, with weight and height in a cohort of healthy 64-107 aged Italian individuals. Notably, two independent meta-analyses of genome-wide association studies found the C-allele of LAMA5 rs4925386-C/T correlated with the risk of colorectal cancer. We tested additional SNPs within the LAMA5 gene for association with anthropometric traits and longevity in our cohort of elderly subjects (N=624). Under an additive model, the rs2427283-C allele (P=0.02) and the rs4925386-T allele (P=0.01) were associated with shorter stature. Age-stratified analyses showed that the rs4925386-T allele was also positively associated with longevity (P=0.001). The association of LAMA5 rs4925386 alleles with both inter-individual differences in height and in longevity suggests that laminins may be among the factors linking stature and cancer susceptibility.
对动物模型和人类的研究表明，生长减缓及成年身高降低与寿命延长有关。此外，流行病学研究报告称成年身高与多种癌症风险之间存在正相关。然而，尚不清楚是哪些因素介导了这些关系。层粘连蛋白是基底膜的主要成分，在细胞增殖和分化过程中与生长因子及基质依赖性受体协同作用。此前，我们报道了编码层粘连蛋白α5链的LAMA5基因中rs659822 - C/T与一组64 - 107岁健康意大利人的体重和身高之间的关联。值得注意的是，两项独立的全基因组关联研究荟萃分析发现，LAMA5 rs4925386 - C/T的C等位基因与结直肠癌风险相关。我们在我们的老年受试者队列（N = 624）中测试了LAMA5基因内的其他单核苷酸多态性（SNP）与人体测量特征和长寿的关联。在加性模型下，rs2427283 - C等位基因（P = 0.02）和rs4925386 - T等位基因（P = 0.01）与较矮的身高相关。年龄分层分析表明，rs4925386 - T等位基因也与长寿呈正相关（P = 0.001）。LAMA5 rs4925386等位基因与个体间身高差异和长寿的关联表明，层粘连蛋白可能是连接身高和癌症易感性的因素之一。
