Journal
DIABETES
Volume 55, Issue 5, Pages 1270-1275Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db05-1498
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Funding
- NCRR NIH HHS [M01 RR 00064, M01 RR000064] Funding Source: Medline
- NHLBI NIH HHS [HL 21088] Funding Source: Medline
- NIDDK NIH HHS [DK 55006, R01 DK055006] Funding Source: Medline
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Adipose triglyceride lipase (ATGL) was recently described to predominantly perform the initial step in triglyceride hydrolysis and therefore seems to play a pivotal role in the lipolytic catabolism of stored fat in adipose tissue. In the first study investigating genetic variations within the ATGL gene in humans, 12 polymorphisms identified via sequencing and database search were studied in 2,434 individuals of European ancestry from Utah. These polymorphisms and their haplotypes were analyzed in subjects not taking diabetes medication for association with plasma free fatty acids (FFAs) as primary analysis, as well as triglycerides and glucose as a secondary analysis (n = 1,701, 2,193, or 2,190, respectively). Furthermore, type 2 diabetes (n = 342 of 2,434) was analyzed as an outcome. FFA concentrations were significantly associated with several single nucleotide polymorphisms (SNPs) of ATGL (P values from 0.015 to 0.00003), consistent with additive inheritance. The pattern was similar when considering triglyceride concentrations. Furthermore, two SNPs showed associations with glucose levels (P < 0.00001) and risk of type 2 diabetes (P < 0.05). Haplotype analysis supported and extended the shown SNP association analyses. These results complement previous findings of functional studies in mammals and elucidate a potential role of ATGL in pathways involved in components of the metabolic syndrome.
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