Journal
DIABETOLOGIA
Volume 51, Issue 1, Pages 62-69Publisher
SPRINGER
DOI: 10.1007/s00125-007-0850-6
Keywords
association; familial combined hyperlipidaemia; gene expression; TCF7L2; triacylglycerol
Categories
Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL028481, R01HL082762] Funding Source: NIH RePORTER
- NATIONAL HUMAN GENOME RESEARCH INSTITUTE [T32HG002536] Funding Source: NIH RePORTER
- NHGRI NIH HHS [T32 HG02536, T32 HG002536] Funding Source: Medline
- NHLBI NIH HHS [HL082762, HL-28481] Funding Source: Medline
Ask authors/readers for more resources
Aims/hypothesis Common DNA variants of the transcription factor 7-like 2 gene (TCF7L2) are associated with type 2 diabetes. Familial combined hyperlipidaemia (FCHL) is characterised by hypertriacylglycerolaemia, hypercholesterolaemia, or both. Additionally, disturbances in glucose metabolism are commonly seen in FCHL. Therefore, we hypothesised that TCF7L2 may contribute to the genetic susceptibility for this common dyslipidaemia. Methods We investigated the effect of the TCF7L2 variants, rs7903146 and rs12255372, on FCHL and its component traits triacylglycerol (TG), total cholesterol (TC) and apolipoprotein B (ApoB) in 759 individuals from 55 Mexican families. As a replication sample, 719 individuals from 60 Finnish FCHL families were analysed. We also used quantitative RT-PCR to evaluate the transcript levels of TCF7L2 in 47 subcutaneous fat biopsies from unrelated Mexican FCHL and normolipidaemic participants. Results Significant evidence for association was observed for high TG for the T alleles of rs7903146 and rs12255372 (p=0.005 and p=0.01) in Mexican FCHL families. No evidence for association was observed for FCHL, TC, ApoB or glucose in Mexicans. When testing rs7903146 and rs12255372 for replication in Finnish FCHL families, these single nucleotide polymorphisms were associated with TG (p=0.01 and p=0.007). urthermore, we observed statistically significant decreases in the mRNA levels (p=0.0002) of TCF7L2 in FCHL- and TG-affected individuals. TCF7L2 expression was not altered by the SNP genotypes. Conclusions/interpretation These data show that rs7903146 and rs12255372 are significantly associated with high TG in FCHL families from two different populations. In addition, significantly decreased expression of TCF7L2 was observed in TG- and FCHL-affected individuals.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available