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


METHODS
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.
Johansen
Christopher T
CT
Robarts Research Institute, University of Western Ontario, London, Canada.
Gallinger
Zane R
ZR
Wang
Jian
J
Ban
Matthew R
MR
Young
T Kue
TK
Bjerregaard
Peter
P
Hegele
Robert A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002318:Cardiovascular Diseases / Q000235:genetics; D005260:Female; D005838:Genotype; D006116:Greenland; D006239:Haplotypes; D006801:Humans; D004930:Inuit / Q000235:genetics*; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood*; D055815:Young Adult; D000217:Acyltransferases
D008049:Lipase; D014280:Triglycerides; C494794:PNPLA2 protein, human; D000217:Acyltransferases