Increased risk of hypercholesterolemia in a French and Lebanese population due to an interaction between rs2569190 in CD14 and gender.

RATIONALE:Since identifying gender-specific genetic associations may have a significant impact on public health, we studied the interaction between rs2569190 in CD14 (cluster of differentiation 14) and gender in relation to the lipid traits in two independent populations. METHODS:We first tested the interaction in a discovery population (SFS, n = 956), then replicated it in an independent population (LGP, n = 460), followed by a meta-analysis (n = 1,416). Finally, stratification according to gender was conducted to test the association between rs2569190 and lipid traits. Binary multiple logistic regression models were used while correcting for many confounders. Power calculations were also performed. RESULTS:An interaction between rs2569190 and gender, which increased the risk of total cholesterol levels in SFS, was found (OR = 2.151 and P = 0.05). This interaction was further replicated in the LGP (OR = 1.353 and P < 0.001), and the meta-analysis showed an overall significant interaction (OR = 1.436 and Pmeta = 0.02). Similarly, the meta-analysis showed an overall significant positive effect (OR = 1.204 and Pmeta = 0.004) for low-density lipoprotein cholesterol levels. Overall, 1,416 patients were evaluated, and the statistical heterogeneity was low, with I2 estimates ranging between 0% and 22.2%. In contrast, rs2569190 in CD14 did not show any significant interaction with gender influencing high-density lipoprotein levels and triglycerides levels in both populations. CONCLUSION:An interaction between rs2569190 in CD14 and gender increased the risk of hypercholesterolemia in two independent populations with a gender-specific effect in males.