Rare ATGL haplotypes are associated with increased plasma triglyceride concentrations in the Greenland Inuit

OBJECTIVES: To genotype common genetic variants found in the adipose triglyceride lipase (ATGL) gene and test them for association with cardiovascular disease risk factors in the Greenland Inuit. STUDY DESIGN: Candidate gene association study of discrete and quantitative traits related to cardiovascular health. METHODS: ATGL was sequenced in 10 European subjects to identify DNA sequence variants. The identified polymorphisms were subsequently genotyped in a population-based cohort of 1,218 unrelated Greenland Inuit subjects, ascertained from the Greenland Population Study. Genotypes and reconstructed haplotypes were tested for association with cardiovascular disease risk factors using additive, dominant or recessive models, corrected for age, sex and body mass index. RESULTS: Five single nucleotide polymorphisms and one 4-base pair deletion were identified in the European sample and were similarly polymorphic in the Greenland Inuit. Independently, variants were not associated with any cardiovascular traits. However, reconstructed rare ATGL haplotypes were associated with increased plasma triglyceride (TG) concentrations compared to the major haplotype under a dominant model (1.21+/-0.7 mmol/L and 1.11+/-0.6 mmol/L, respectively, p=0.006). CONCLUSIONS: Rare ATGL haplotypes are associated with increased plasma TG concentrations in the Greenland Inuit.