Evaluating the Association of FAAH Common Gene Variation with Childhood, Adult Severe Obesity and Type 2 Diabetes in the French Population

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Abstract

Objective:

The endocannabinoid pathway is involved in eating behavior and body weight regulation in both animals and humans. The association of a missense polymorphism (Pro129Thr) in FAAH gene with overweight/obesity has been recently questioned.

Subjects and Methods:

To evaluate the contribution of the FAAH gene variation in polygenic obesity and type 2 diabetes mellitus (T2DM) in the French population, we investigated the entire FAAH locus. We selected and genotyped ten tagged single nucleotide polymorphisms (SNPs) in 635 obese children, 896 morbidly obese adults, 2,238 T2DM subjects and 1,340 control subjects, all of French European origin. Case control association tests were performed using logistic regression models.

Results:

Nominal evidences of association were observed for rs6429600, rs324419, rs324418, rs2295633, rs7520850 and risk for class III adult obesity (0,001 < p < 0.04). The rs324420 (Pro129Thr) was nominally associated with class III adult obesity (ORadditive = 0.79 (95% CI 0.67-0.93), p = 0.005; ORdominant = 0.76 (95% CI 0.63-0.92), p = 0.005), Pro129 being the obesity risk allele. These associations did not remain significant after Bonferroni correction for multiple testing. There was no significant association between FAAH SNPs and risk for childhood obesity or T2DM.

Conclusion:

Our results in 5,109 subjects suggest that FAAH Pro129Thr polymorphism may modestly contribute to class III adult obesity in the French population. Further validation is needed to precise the role of this gene variant in obesity susceptibility background.

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