CETP variant rs6499861 lowers HDL cholesterol more strongly in obese Korean men and women with a family history of diabetes (J Lipid Atheroscler 2019)

Objectives: The aim of this study was to examine the associations of cholesterol ester transfer protein (CETP) rs6499861 and rs12708980 with high-density lipoprotein cholesterol (HDL-C) considering obesity and family history of diabetes (FHD) in Korean men and women.

Methods: We analyzed the association of CETP single nucleotide polymorphisms (SNPs) with HDL-C among individuals selected from a hospital (n=4 294) and the Bundang-gu area in Korea (n=2 304).

Results: We found that the CETP SNP rs6499861 was associated with a lower HDL-C level (effect per allele: -2.044 mg/dL, p<0.0001). Individuals with a rs6499861 CG/GG genotype had a 1.45-fold higher risk of an abnormal level of HDL-C (<40 mg/dL) than those with a CC genotype. This genotype-HDL-C association was stronger in women (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.39-2.85) compared with men (OR, 1.33; 95% CI, 1.10-1.61) and in women with a FHD (OR, 4.82; 95% CI, 1.86-12.5; p=0.0012) compared with women without a family history. Relative to individuals with a CC genotype and body mass index (BMI) <25.69 kg/m2, individuals with a CG/GG genotype and BMI ≥25.69 kg/m2 had an OR (95% CI) of 2.61 (1.97-3.47).

Conclusions: These findings indicate that CETP variants are linked to HDL-C level in Koreans and that this link is stronger in obese men and in women who have a FHD.