New approaches to determine which common genetic variants may be responsible for lipid disorders within the wider population particularly the association between clinical phenotype and single nucleotide polymorphisms (SNPs) or genetic loci in multiple genes. These systematic genome-wide association studies (GWAS) have identified several new loci. At 5 loci the same SNP identified in whites was found to be significantly associated with blood lipids across all ethnic groups. At 1p13 near PSRC1/CELSR2/SORT1, rs646776 and at HMGCR, rs12654264 were associated with LDL-C. In all groups each copy of the minor G allele in polymorphism rs646776 lowered LDL-C. SNPs, r1800775 at CETP and rs328 at LPL were associated with HDL-C. Increases in minor allele copy number of r1800775 and rs328 resulted in decreases and increases in HDL-C respectively. At APOA5, increase in minor allele copy number of rs3135506 was associated with increases in triglyceride levels. This indicates that all 5 loci are important for controlling lipid profiles across ethnic/racial groups and highlight the relevance of the newly discovered locus at 1p13 near PSRC1/CELSR2/SORT1. GWA studies have also identified common variants in the fat mass and obesity (FTO) gene associated with body mass index (BMI) and increased risk of obesity. The rs9939609 A allele was found to be associated with increased BMI, lower plasma HDL-C levels, higher plasma triglycerides, greater atherogenic markers and increased risk of myocardial infarction. The increased risk of MI was abolished by statin use suggesting the FTO genotype may provide a therapeutic target.
- dyslipidemia genes
- molecular biology