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Anthropometry, Carbohydrate and Lipid Metabolism in the East Flanders Prospective Twin Survey: Linkage of Candidate Genes Using Two Sib-Pair Based Variance Components Analyses

Published online by Cambridge University Press:  21 February 2012

Nicole Y. Souren ,
Maurice P. Zeegers ,
Rob G. J. H. Janssen ,
Anja Steyls ,
Marij Gielen ,
Ruth J. F. Loos ,
Gaston Beunen ,
Robert Fagard ,
Alphons P. M. Stassen  and
Jeroen Aerssens
...Show all authors
Nicole Y. Souren*
Affiliation:
Department of Complex Genetics, Maastricht University, the Netherlands; Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, United Kingdom. Nicole.Souren@GEN.unimaas.nl
Maurice P. Zeegers
Affiliation:
Department of Complex Genetics, Maastricht University, the Netherlands; Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, United Kingdom.
Rob G. J. H. Janssen
Affiliation:
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Genome Center Maastricht, Maastricht University, the Netherlands.
Anja Steyls
Affiliation:
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Division of Clinical Genetics, Academic Hospital Maastricht, the Netherlands.
Marij Gielen
Affiliation:
Department of Complex Genetics, Maastricht University, the Netherlands; Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Unit of Genetic Epidemiology, Department of Public Health and Epidemiology, University of Birmingham, United Kingdom.
Ruth J. F. Loos
Affiliation:
Medical Research Council Epidemiology Unit, Cambridge, United Kingdom; Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Belgium.
Gaston Beunen
Affiliation:
Department of Biomedical Kinesiology, Faculty of Kinesiology and Rehabilitation Sciences, Katholieke Universiteit Leuven, Belgium.
Robert Fagard
Affiliation:
Hypertension and Cardiovascular Rehabilitation Unit, Department of Cardiovascular Diseases, Katholieke Universiteit Leuven, Belgium.
Alphons P. M. Stassen
Affiliation:
Division of Clinical Genetics, Academic Hospital Maastricht, the Netherlands.
Jeroen Aerssens
Affiliation:
Department of Internal Medicine, Johnson & Johnson Pharmaceutical Research & Development, Belgium.
Catherine Derom
Affiliation:
Department of Human Genetics, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium.
Robert Vlietinck
Affiliation:
Department of Human Genetics, Faculty of Medicine, Katholieke Universiteit Leuven, Belgium.
Aimee D. C. Paulussen
Affiliation:
Nutrition and Toxicology Research Institute Maastricht (NUTRIM), Maastricht University, the Netherlands; Division of Clinical Genetics, Academic Hospital Maastricht, the Netherlands.
*
*Address for correspondence: NYP Souren, MSc, Maastricht University, Department of Complex Genetics, Universiteitssingel 50, 6200 MD, Maastricht, The Netherlands.

Abstract

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Insulin resistance and obesity are underlying causes of type 2 diabetes and therefore much interest is focused on the potential genes involved. A series of anthropometric and metabolic characteristic were measured in 240 MZ and 112 DZ twin pairs recruited from the East Flanders Prospective Twin Survey. Microsatellite markers located close to ABCC8, ADIPOQ, GCK, IGF1, IGFBP1, INSR, LEP, LEPR, PPARγ and the RETN gene were genotyped. Univariate single point variance components linkage analyses were performed using two methods: (1) the standard method, only comprising the phenotypic and genotypic data of the DZ twin pairs and (2) the extended method, also incorporating the phenotypic data of the MZ twin pairs. Suggestive linkages (LOD > 1) were observed between the ABCC8 marker and waist-to-hip ratio and HDL-cholesterol levels. Both markers flanking ADIPOQ showed suggestive linkage with triglycerides levels, the upstream marker also with body mass and HDL-cholesterol levels. The IGFBP1 marker showed suggestive linkage with fat mass, fasting insulin and leptin levels and the LEP marker showed suggestive linkage with birth weight. This study suggests that DNA variants in ABCC8, ADIPOQ, IGFBP1 and LEP gene region may predispose to type 2 diabetes. In addition, the two methods used to perform linkage analyses yielded similar results. This was however not the case for birth weight where chorionicity seems to be an important confounder.

Keywords

East Flanders Prospective Twin SurveyType 2 diabetesObesityDyslipidaemiaLinkageCandidate Genes
Type
Articles
Information
Twin Research and Human Genetics , Volume 11 , Issue 5 , 01 October 2008 , pp. 505 - 516
Copyright
Copyright © Cambridge University Press 2008