Original Article

International Journal of Obesity (2006) 30, 892–898. doi:10.1038/sj.ijo.0803234; published online 24 January 2006

The Gln223Arg polymorphism in the leptin receptor is associated with familial combined hyperlipidemia

G M van der Vleuten1, L A Kluijtmans2, A Hijmans1, H J Blom2, A F H Stalenhoef1 and J de Graaf1

  1. 1Department of Medicine, Division of General Internal Medicine, Nijmegen, The Netherlands
  2. 2Department of Pediatrics and Neurology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands

Correspondence: GM van der Vleuten, Department of Medicine, Division of General Internal Medicine, 463, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, The Netherlands. E-mail: G.vandervleuten@aig.umcn.nl

Received 4 June 2005; Revised 29 October 2005; Accepted 8 December 2005; Published online 24 January 2006.

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Abstract

Objective:

 

Familial combined hyperlipidemia (FCH) is characterized by elevated levels of total cholesterol (TC), triglycerides (TG) and apolipoprotein B (apo B) and is associated with premature cardiovascular disease (CVD). Other features of FCH are obesity and insulin resistance. Serum leptin levels have also been associated with obesity, insulin resistance and atherosclerosis. Leptin exerts its effect through the leptin receptor (LEPR). The aim of this study is to determine whether the Gln223Arg polymorphism in the LEPR gene contributes to FCH and its associated phenotypes.

Methods:

 

The study population consists of 37 families, comprising 644 subjects, of whom 158 subjects were diagnosed as FCH. The FCH diagnosis was based on plasma TC and TG levels, adjusted for age and gender, and absolute apo B levels, according to our recently published nomogram. The Gln223Arg polymorphism was studied by restriction fragment length polymorphism-PCR.

Results:

 

Carriers of one or two Arg alleles had an increased risk of FCH, compared to subjects homozygous for the Gln allele (OR=1.6 [95% CI 1.0–2.4]). A difference in high-density lipoprotein cholesterol (HDL-c) levels was present between carriers and non-carriers of an Arg allele, 1.21 vs 1.28 mmol/l, respectively (P=0.04), but no differences in obesity, insulin resistance and other lipid parameters were found.

Conclusion:

 

The Gln223Arg polymorphism in the LEPR gene is associated with FCH, which is supported by a significant association between HDL-c levels and the LEPR gene.

Keywords:

familial combined hyperlipidemia, leptin receptor, polymorphism, lipids, HDL-cholesterol

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