Johansen Christopher T, Gallinger Zane R, Wang Jian, Ban Matthew R, Young T Kue, Bjerregaard Peter, Hegele Robert A
Robarts Research Institute, University of Western Ontario, London, Canada.
Int J Circumpolar Health. 2010 Feb;69(1):3-12. doi: 10.3402/ijch.v69i1.17427.
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.
Candidate gene association study of discrete and quantitative traits related to cardiovascular health.
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.
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).
Rare ATGL haplotypes are associated with increased plasma TG concentrations in the Greenland Inuit.
对脂肪甘油三酯脂肪酶（ATGL）基因中发现的常见基因变异进行基因分型，并检测它们与格陵兰因纽特人心血管疾病风险因素的关联。
对与心血管健康相关的离散和定量性状进行候选基因关联研究。
对10名欧洲受试者的ATGL进行测序，以鉴定DNA序列变异。随后，在从格陵兰岛人口研究中确定的1218名无亲缘关系的格陵兰因纽特人群体队列中，对鉴定出的多态性进行基因分型。使用加性、显性或隐性模型，对年龄、性别和体重指数进行校正，检测基因型和重建单倍型与心血管疾病风险因素的关联。
在欧洲样本中鉴定出5个单核苷酸多态性和1个4碱基对缺失，在格陵兰因纽特人中也有类似的多态性。单独来看，这些变异与任何心血管性状均无关联。然而，在显性模型下，与主要单倍型相比，重建的罕见ATGL单倍型与血浆甘油三酯（TG）浓度升高相关（分别为1.21±0.7 mmol/L和1.11±0.6 mmol/L，p=0.006）。
在格陵兰因纽特人中，罕见的ATGL单倍型与血浆TG浓度升高相关。
