Association between CETP, MLXIPL, and TOMM40 polymorphisms and serum lipid levels in a Latvian population

Abnormal lipid levels are considered one of the most significant risk factors for atherosclerosis and coronary artery disease, two of the main causes of death worldwide. Apart from monogenic cases of hypercholesterolemia, most of the common dyslipidemias are caused by a number of low-impact polymorphisms. It has recently been reported that frequent polymorphisms at a large number of loci are significantly associated with one or more blood lipid parameters in many populations. Identifying these associations in different populations and estimating the possible interactions between genetic models are necessary to explain the underlying genetic architecture of the associated loci and their ultimate impact on lipid-associated traits.

We estimated the association between 144 common single-nucleotide polymorphisms (SNPs) from published genome-wide association studies and the levels of total cholesterol, low- and high-density lipoprotein-cholesterol, and triglycerides in 1273 individuals from the Genome Database of the Latvian Population. We analyzed a panel of 144 common SNPs with Illumina GoldenGate Genotyping Assays on the Illumina BeadXpress System.

Ten SNPs at the CETP locus and two at the MLXIPL locus were associated with reduced high-density lipoprotein-cholesterol levels; one SNP at the TOMM40 locus was associated with increased low-density lipoprotein-cholesterol; and four SNPs at the MLXIPL locus were associated with increased log triglyceride levels. There was also a significant correlation between the number of risk alleles and all the lipid parameters, suggesting that the coexistence of many low-impact SNPs has a greater effect on the dyslipidemia phenotype than the individual effects of found SNPs.

We conclude that the CETP, MLXIPL, and TOMM40 loci are the strongest genetic factors underlying the variability in lipid traits in our population.