Association of common polymorphisms in the fractalkine receptor (CX3CR1) with obesity

The inflammatory component in obesity is now well established. The CX3CR1 gene encodes the fractalkine (CX3CL1) receptor and has two coding single-nucleotide polymorphisms, V249I and T280M, linked to a lower risk of other inflammatory diseases such as coronary artery disease (CAD) and asthma. To determine whether CX3CR1 is associated with obesity, we genotyped the V249I and T280M polymorphisms of the CX3CR1 gene in subjects with a BMI ≥30 kg/m² and nonobese controls with a BMI <30 kg/m². Binary logistic regression analyses revealed that the 280MM genotype was associated with obesity (P = 0.022). A gender-specific one-way ANOVA was also conducted to investigate mean BMI and waist circumference differences between genotypes of each polymorphism. For both polymorphisms independently, women carrying two copies of the minor allele had significant higher mean waist circumference than those carrying only one copy of the minor allele (MM > TM, P = 0.031; II > VI, P = 0.013) or those who were homozygous for the major allele (MM > TT, P = 0.005; II > VV, P = 0.006). We also observed significant higher mean waist circumference in men carrying one copy of the minor allele when compared to those who were homozygous for the major allele for the T280M polymorphism (TM > TT, P = 0.029). This study suggests that CX3CR1, a biomarker of obesity in this sample, constitutes a potential target for further investigation of the role of inflammation in the expression of obesity-related phenotypes.