Studies in animal models and humans suggest that reduced growth and adult statureare associated with lifespan extension. Moreover, epidemiological studiesreported a positive association between adult height and risk of multiplecancers. Yet, it is unclear which factors mediate these relationships. Lamininsare 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 thelaminin-α5 chain, with weight and height in a cohort of healthy 64-107 agedItalian individuals. Notably, two independent meta-analyses of genome-wideassociation studies found the C-allele of LAMA5 rs4925386-C/T correlated with therisk of colorectal cancer. We tested additional SNPs within the LAMA5 gene forassociation with anthropometric traits and longevity in our cohort of elderlysubjects (N=624). Under an additive model, the rs2427283-C allele (P=0.02) andthe rs4925386-T allele (P=0.01) were associated with shorter stature.Age-stratified analyses showed that the rs4925386-T allele was also positivelyassociated with longevity (P=0.001). The association of LAMA5 rs4925386 alleleswith both inter-individual differences in height and in longevity suggests thatlaminins may be among the factors linking stature and cancer susceptibility.

Association of the Laminin, Alpha 5 (LAMA5) rs4925386 with height and longevity in an elderly population from Southern Italy.

De Rango, Francesco;PASSARINO, Giuseppe;ROSE, Giuseppina
2016

Abstract

Studies in animal models and humans suggest that reduced growth and adult statureare associated with lifespan extension. Moreover, epidemiological studiesreported a positive association between adult height and risk of multiplecancers. Yet, it is unclear which factors mediate these relationships. Lamininsare 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 thelaminin-α5 chain, with weight and height in a cohort of healthy 64-107 agedItalian individuals. Notably, two independent meta-analyses of genome-wideassociation studies found the C-allele of LAMA5 rs4925386-C/T correlated with therisk of colorectal cancer. We tested additional SNPs within the LAMA5 gene forassociation with anthropometric traits and longevity in our cohort of elderlysubjects (N=624). Under an additive model, the rs2427283-C allele (P=0.02) andthe rs4925386-T allele (P=0.01) were associated with shorter stature.Age-stratified analyses showed that the rs4925386-T allele was also positivelyassociated with longevity (P=0.001). The association of LAMA5 rs4925386 alleleswith both inter-individual differences in height and in longevity suggests thatlaminins may be among the factors linking stature and cancer susceptibility.
Aging, Extracellular matrix, Height, Laminins, Longevity
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/20.500.11770/142768
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