Genetic variants near the MGAT1 gene are associated with body weight, BMI and fatty acid metabolism among adults and children

Objective:Recently a genome-wide association analysis from five European populations identified a polymorphism located downstream of the mannosyl-(α-1,3)-glycoprotein-Β-1,2-N-acetylglucosaminyltransferase (MGAT1) gene that was associated with body-weight. In the present study, associations between MGAT1 variants combined with obesity and insulin measurements were investigated in three cohorts. Levels of fatty acids and estimated measures of Δ desaturases were also investigated among adult men.Design:Six polymorphisms downstream of MGAT1 were genotyped in a cross-sectional cohort of 1152 Swedish men. Three polymorphisms were further analyzed in a case-control study of 1076 Swedish children and in a cross-sectional study of 2249 Greek children.Results:Three polymorphisms, rs12186500 (odds ratio (OR): 1.892, 95 confidence interval (CI): 1.237-2.895, P=0.003), rs1021001 (OR: 2.102, 95 CI: 1.280-3.455, P=0.003) and rs4285184 (OR: 1.587, 95 CI: 1.024-2.459, P=0.038) were associated with a higher prevalence of obesity among the adult men and a trend for obesity was observed for rs4285184 among the Swedish (OR: 1.205, 95 CI: 0.987-1.471, P=0.067) and Greek children (OR: 1.192, 95CI: 0.978-1.454, P=0.081). Association with body weight was observed for rs12186500 (P=0.017) and rs4285184 (P=0.024) among the men. The rs1021001 and rs4285184 were also associated with body mass index (BMI) in the two Swedish cohorts and similar trends were observed among the Greek children. The combined effect size for rs1021001 and rs4285184 on BMI z-score from a meta-analysis was 0.233 (95 CI:0.093-0.373, P=0.001) and 0.147 (95 CI:0.057-0.236, P=0.001), respectively. We further observed associations between the genetic variants and fatty acids (P<0.039) and estimated measures of Δ desaturases (P<0.040), as well as interactions for rs12186500 (P<0.019) with an effect on BMI. No association was found with homeostatic model assessment-insulin resistance in any cohort but increased insulin levels, insulin response and decreased insulin sensitivity were observed among the children (P<0.038).Conclusion:Genetic variants downstream MGAT1 seem to influence susceptibility to obesity. Moreover, these genetic variants affect the levels of serum unsaturated fatty acids and Δ desaturase indices, variables previously shown to correlate with obesity. © 2012 Macmillan Publishers Limited All rights reserved

The correlation of right 2D:4D finger length ratio to the low-grade inflammation marker IL-6 in children: The healthy growth study

Background: Second to fourth digit ratio (2D:4D) is associated with cardiometabolic risk in adults. Aim: To examine the association of right 2D:4D with cardiovascular disease risk factors in children. Study design: Cross-sectional study. Subjects: A sample of 301 children (53.5% girls) aged 9-13 in Greece and their parents. Children who were sick during the previous week of examination (n = 44) were excluded from the analyses. Outcome measures: Socio-demographic (gestational age, birth weight, age, gender, maternal education level), anthropometric (body weight and height, finger length), clinical (pubertal stage, sickness during the previous week of the examination), blood [serum high sensitivity C-reactive protein (CRP), serum high sensitivity interleukin-6 (IL-6), serum leptin], lifestyle (dietary intake, maternal smoking during pregnancy) and physical fitness (handgrip strength) data were collected. CRP, IL-6 and leptin were measured with ELISA, using standard equipment and procedures, in accordance with manufacturers' instructions. Results: Full data were available for 257 children (52.1% girls). The rank values of right 2D:4D and IL-6 were included in the analyses. Right 2D:4D was correlated only with IL-6 at a bivariate level (r = 0.216, p = 0.012) in girls. At a linear multivariate level, this association remained significant, even after adjusting for several potential confounders such as age, Tanner stage, maternal education level, body mass index, maternal smoking during pregnancy, duration of pregnancy, protein-, carbohydrate-, fat-intake and physical fitness (β ± SE = 0.220 ± 0.066, p = 0.001). Conclusions: Right 2D:4D was found to be associated with IL-6 in girls. Right 2D:4D may be a valuable, simple screening tool of low-grade inflammation in children. © 2013 Elsevier Ltd