1. ^*Lipid Research Center, Nutraceuticals and Functional Foods Institute and Department of Food Sciences and Nutrition, Laval University, Ste-Foy, Quebec, Canada
2. ^§Department of Social and Preventive Medicine, Laval University, Ste-Foy, Quebec, Canada
3. ^†Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
4. ^‡Psychiatric Genetic Unit, Laval University Robert-Giffard Research Center, Quebec, Canada

Correspondence: Louis Pérusse Division of Kinesiology, Department of Social and Preventive Medicine, Faculty of Medicine, Laval University, Ste-Foy, Quebec, Canada G1K 7P4. E-mail: louis.perusse@kin.msp.ulaval.ca

^*The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 14 July 2006; Revised  0000; Accepted 15 January 2007.

Abstract

Objective: In the present study, we undertook a two-step fine mapping of a 20-megabase region around a quantitative trait locus previously reported on chromosome 15q26 for abdominal subcutaneous fat (ASF) in an extended sample of 707 subjects from 202 families from the Quebec Family Study.

Research Methods and Procedure: First, 19 microsatellites (in addition to the 7 markers initially available on 15q24-q26; total = 26) were genotyped and tested for linkage with abdominal total fat, abdominal visceral fat, and ASF assessed by computed tomography and with fat mass (FM) using variance component-based approach on age- and sex-adjusted phenotypes. Second, 16 single nucleotide polymorphisms (SNPs) were genotyped and tested for association using family-based association tests.

Results: After the fine mapping, the peak logarithm of odds ratio (LOD) score (marker D15S1004) increased from 2.79 to 3.26 for ASF and from 3.52 to 4.48 for FM, whereas for abdominal total fat, the peak linkage (marker D15S996) decreased from 2.22 to 1.53. No evidence of linkage was found for abdominal visceral fat. Overall, for genotyped SNPs, three variants located in the putative MCTP2 gene were significantly associated with FM and the three abdominal fat phenotypes (p 0.05). The major allele and genotype of rs1424695 were associated with higher adiposity values (p < 0.004). The same trend was found for the two other polymorphisms (p < 0.05). None of the other SNPs was associated with adiposity phenotypes. The linkage for FM became non-significant (LOD = 0.84) after adjustment for the MCTP2 polymorphisms, whereas the one for ASF remained unchanged.

Discussion: These results suggest that the MCTP2 gene, located on chromosome 15q26, influences adiposity. Other studies will be needed to investigate the function of the MCTP2 gene and its role in obesity.