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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.

SUBMITTER: De Luca M

PROVIDER: S-EPMC5020947 | biostudies-other | 2012 Dec

REPOSITORIES: biostudies-other

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Project description:Previous studies have demonstrated a positive relationship between liver cancer and diabetes mellitus. However, elevated fasting blood glucose (FBG) itself may be a risk factor for the development of hepatocellular carcinoma (HCC) rather than diabetes, and during the follow-up period, death is an event that may occur before the occurrence of HCC, which should be dealt with competing risk models. Our study aims to investigate the relationship between FBG and new-onset HCC by using competing risk regression models.We prospectively studied the relationship between FBG concentrations and risk of HCC in a cohort of 93,447 participants who were free of prior HCC, and whose demographic characteristics and biochemical parameters were recorded. Cox proportional hazards regression models and competing risk regression models were used to evaluate the association between FBG concentrations and risk of incident HCC.A total of 302 participants were diagnosed with HCC among 93,447 subjects during 810,499 person-years of follow-up. The multivariable hazard ratios (HRs) [95% confidence interval (95% CI)] for the association of FBG and log(FBG) with HCC were 1.07 (1.01∼1.12), 1.84 (1.23∼2.74) in an analysis adjusted for other potential variables. In the multivariable adjusted analysis, participants who were in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group would have increased the risk of HCC by 47% and 69%, respectively. In a cause-specific hazard model (CS model), the multivariable HRs (95% CI) for the association of FBG with HCC were 1.46 (1.09∼1.98), 1.69 (1.27∼2.27) in the multivariable adjusted analysis. Similar results were also observed in sub-distribution hazard function model (SD model) with corresponding multivariate HRs (95% CI) of 1.46 (1.09∼2.00), 1.69 (1.25∼2.27) in 4.82 mmol/L≤FBG≤5.49 mmol/L group and FBG >5.49 mmol/L group, respectively.Higher FBG concentrations itself were positively associated with new-onset HCC in the Cox proportional hazards regression models and competing risk models. FBG concentrations can be used as a scientific and important way to identify individuals with a higher risk of HCC and control of FBG concentrations might serve as a possible way to decrease the risk of HCC among Chinese population.Trial registration: ChiCTR-TNRC-11001489. Registered August 24, 2011 (retrospectively registered).

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

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