TY - JOUR
T1 - TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia
AU - Huertas-Vazquez, A.
AU - Plaisier, C.
AU - Weissglas-Volkov, D.
AU - Sinsheimer, J.
AU - Canizales-Quinteros, S.
AU - Cruz-Bautista, I.
AU - Nikkola, E.
AU - Herrera-Hernandez, M.
AU - Davila-Cervantes, A.
AU - Tusie-Luna, T.
AU - Taskinen, M. R.
AU - Aguilar-Salinas, C.
AU - Pajukanta, P.
N1 - Funding Information:
Acknowledgements We thank the family members for their participation in this study. L. Peltonen is thanked for sample collection. We also thank M. Lupsakko, L. Riba and S. Ramirez for laboratory technical assistance. This research was supported by US National Institutes of Health grants HL082762, HL-28481, as well as by American Heart Association grant 0430180N. A. Huertas-Vazquez was supported by American Heart Association grant 0725232Y. D. Weissglas-Volkov and C. Plaisier were supported by National Human Genome Research Institute grant T32 HG02536.
PY - 2008/1
Y1 - 2008/1
N2 - 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). Furthermore, 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.
AB - 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). Furthermore, 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.
KW - Association
KW - Familial combined hyperlipidaemia
KW - Gene expression
KW - TCF7L2
KW - Triacylglycerol
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U2 - 10.1007/s00125-007-0850-6
DO - 10.1007/s00125-007-0850-6
M3 - Article
C2 - 17972059
AN - SCOPUS:36649027501
SN - 0012-186X
VL - 51
SP - 62
EP - 69
JO - Diabetologia
JF - Diabetologia
IS - 1
ER -