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Background  The apolipoprotein E ( APOE ) gene is polymorphic, encoding one of 3 common alleles (ε2, ε3, ε4) produced from combinations of 2 non-synonymous SNPs (rs429358 and rs7412). APOE plays an important role controlling plasma lipids but its association with adipocyte functionality and body fatness remains to be determined.    Methods  We analyzed fasting plasma lipids and genotyped the two main  APOE -SNPs (rs429358 and rs7412), both located in the fourth exon of the  APOE , in 4660 Caucasian middle-aged men free of cardiovascular disease.    Results  The rs7412 SNP, which determines the APOE2 isoform, was significantly associated with Body Mass Index (BMI) and Waist Girth (WG) in a multivariate model accounting for age, smoking status and plasma lipids. BMI and WG were highest in TT homozygotes and lowest in CC homozygotes. This effect was independent of the rs429358 SNP, which failed to show any association with the BMI and WG variables. The odds ratio of being obese (BMI>30) for individuals carrying the APOε2 allele, present in 14% of the cohort and defined by the rs7412 SNP, was also significant in this multivariate model, with an OR of 1.27 (95% CI: 1.01–1.59).    Conclusions  This study provides an evidence of a lipid-independent association between the APOE SNP rs7412 and body fatness surrogates, BMI and WG, in a large cohort of middle-aged males.

The Apolipoprotein E Polymorphism rs7412 Associates with Body Fatness Independently of Plasma Lipids in Middle Aged Men