A nonsynonymous SNP in BANK1 is associated with serum LDL cholesterol levels in three Korean populations

Serum levels of lipids, such as cholesterol and triglycerides, are heritable risk factors for cardiovascular disease and targets for therapeutic intervention. because previous genome-wide association studies (gwass) did not target functional genetic variants, we employed an alternate approach using nonsynonymous single-nucleotide polymorphisms (snps) to identify functional genetic variants associated with the regulation of serum lipid levels. we selected 3667 healthy individuals from a rural community-based cohort (cavas; cardio vascular disease association study) of the korean genome and epidemiology study project. we analyzed demographic and lifestyle information, lipid measurements and genotypes using the illumina-1m snp chip. for genotyping, we isolated 11 558 nonsynonymous snps and conducted a linear regression analysis with four lipid traits (total, high-density lipoprotein (hdl) and low-density lipoprotein (ldl) cholesterols and triglycerides). significantly associated snps were validated in two independent korean populations, korean association resource (kare) (n=4116) and health examinee (hexa) (n=2178). of the 11 558 snps, one snp (rs3733197) from the cavas was significantly associated with serum ldl cholesterols (beta±s.e.=4.67±0.94, p-value=1.0 × 10−6 and bonferroni corrected p-value=0.012). the replication results of hexa and kare were beta±s.e.=2.88±1.12, p-value=0.016 and beta±s.e.=1.26±0.97, p-value=0.196, respectively. an overall meta-analysis of the three data sets revealed beta=2.98±0.57, p-value=6.19 × 10−7. the rs3733197 is located in the coding region of bank1 (b-cell scaffold protein with ankyrin repeats 1), and the minor allele (a) resulted in the replacement of the alanine at position 383 with threonine.