TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia

A. Huertas-Vazquez, Christopher Plaisier, D. Weissglas-Volkov, J. Sinsheimer, S. Canizales-Quinteros, I. Cruz-Bautista, E. Nikkola, M. Herrera-Hernandez, A. Davila-Cervantes, T. Tusie-Luna, M. R. Taskinen, C. Aguilar-Salinas, P. Pajukanta

Research output: Contribution to journalArticle

40 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)62-69
Number of pages8
JournalDiabetologia
Volume51
Issue number1
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

T Cell Transcription Factor 1
Familial Combined Hyperlipidemia
Adipose Tissue
Triglycerides
Serum
Genes
Apolipoproteins B
Single Nucleotide Polymorphism
Cholesterol
Glucose
Subcutaneous Fat
Genetic Predisposition to Disease
Dyslipidemias
Hypercholesterolemia
Type 2 Diabetes Mellitus

Keywords

  • Association
  • Familial combined hyperlipidaemia
  • Gene expression
  • TCF7L2
  • Triacylglycerol

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Huertas-Vazquez, A., Plaisier, C., Weissglas-Volkov, D., Sinsheimer, J., Canizales-Quinteros, S., Cruz-Bautista, I., ... Pajukanta, P. (2008). TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia. Diabetologia, 51(1), 62-69. https://doi.org/10.1007/s00125-007-0850-6

TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia. / Huertas-Vazquez, A.; Plaisier, Christopher; Weissglas-Volkov, D.; Sinsheimer, J.; Canizales-Quinteros, S.; Cruz-Bautista, I.; Nikkola, E.; Herrera-Hernandez, M.; Davila-Cervantes, A.; Tusie-Luna, T.; Taskinen, M. R.; Aguilar-Salinas, C.; Pajukanta, P.

In: Diabetologia, Vol. 51, No. 1, 01.01.2008, p. 62-69.

Research output: Contribution to journalArticle

Huertas-Vazquez, A, Plaisier, C, Weissglas-Volkov, D, Sinsheimer, J, Canizales-Quinteros, S, Cruz-Bautista, I, Nikkola, E, Herrera-Hernandez, M, Davila-Cervantes, A, Tusie-Luna, T, Taskinen, MR, Aguilar-Salinas, C & Pajukanta, P 2008, 'TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia', Diabetologia, vol. 51, no. 1, pp. 62-69. https://doi.org/10.1007/s00125-007-0850-6
Huertas-Vazquez, A. ; Plaisier, Christopher ; Weissglas-Volkov, D. ; Sinsheimer, J. ; Canizales-Quinteros, S. ; Cruz-Bautista, I. ; Nikkola, E. ; Herrera-Hernandez, M. ; Davila-Cervantes, A. ; Tusie-Luna, T. ; Taskinen, M. R. ; Aguilar-Salinas, C. ; Pajukanta, P. / TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia. In: Diabetologia. 2008 ; Vol. 51, No. 1. pp. 62-69.
@article{1cb83ebbbdc14e9f8f402e42debb9fe5,
title = "TCF7L2 is associated with high serum triacylglycerol and differentially expressed in adipose tissue in families with familial combined hyperlipidaemia",
abstract = "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.",
keywords = "Association, Familial combined hyperlipidaemia, Gene expression, TCF7L2, Triacylglycerol",
author = "A. Huertas-Vazquez and Christopher Plaisier and D. Weissglas-Volkov and J. Sinsheimer and S. Canizales-Quinteros and I. Cruz-Bautista and E. Nikkola and M. Herrera-Hernandez and A. Davila-Cervantes and T. Tusie-Luna and Taskinen, {M. R.} and C. Aguilar-Salinas and P. Pajukanta",
year = "2008",
month = "1",
day = "1",
doi = "10.1007/s00125-007-0850-6",
language = "English (US)",
volume = "51",
pages = "62--69",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "1",

}

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, Christopher

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.

PY - 2008/1/1

Y1 - 2008/1/1

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

UR - http://www.scopus.com/inward/record.url?scp=36649027501&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=36649027501&partnerID=8YFLogxK

U2 - 10.1007/s00125-007-0850-6

DO - 10.1007/s00125-007-0850-6

M3 - Article

C2 - 17972059

AN - SCOPUS:36649027501

VL - 51

SP - 62

EP - 69

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 1

ER -