Common variants in the LAMA5 gene associate with fasting plasma glucose and serum triglyceride levels in a cohort of pre- and early pubertal children

Abstract

Laminins are glycoproteins found in basement membranes where they play a vital role in tissue architecture and cell behavior. Previously, we reported the association of two polymorphisms (rs659822 and rs944895) in the laminin alpha5 (LAMA5) gene with anthropometric traits, fasting lipid profile, and glucose levels in pre-menopausal women and elderly subjects. Furthermore, studies in mice showed that Lama5 is involved in organogenesis and placental function during pregnancy. The objective of this study was to investigate whether rs659822 and/or rs944895 are associated with inter-individual variability in birth weight as well as anthropometric traits and metabolic phenotypes in children. Two hundred and eighty nine healthy children aged 7–12 yr of European, Hispanic, and African-American ancestry were studied. Co-dominant models adjusted for genetic admixture, age, gender, and stages of puberty were used to test for the association of the polymorphisms with each trait. Our analysis showed significant associations of rs659822 with fasting plasma glucose levels (P = 0.0004) and of rs944895 with fasting serum triglycerides (P = 0.004) after Bonferroni correction for multiple testing. Our results corroborate our previous findings that genetic variants in LAMA5 contribute to variation in metabolic phenotypes and provide evidence that this may occur early in life.

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