Evidence for a gene influencing high-density lipoprotein cholesterol on chromosome 4q31.21

Zari Dastani, Leigh Quiogue, Christopher Plaisier, James C. Engert, Michel Marcil, Jacques Genest, Päivi Pajukanta

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Objective - A low level of plasma high-density lipoprotein cholesterol (HDL-C) is a major risk factor for coronary atherosclerosis. To identify novel genes regulating plasma HDL-C levels, we investigated 13 multigenerational French Canadian families with an average of 12 affected individuals per family for genome-wide signals, which we subsequently fine mapped. Methods and Results - We genotyped a total of 362 individuals, including 151 affected subjects for 485 autosomal microsatellite markers. In parametric 2-point linkage analyses, the highest 2-point logarithm of odds (lod) score of 4.6 was observed with marker D4S424 on chromosome 4q31.21 (at ≈142 Mb). The multipoint analysis of this region resulted in a lod score of 3.8 and a lod -1 region of 12.2 cM, containing 40 known genes. The results were obtained by allowing for genetic heterogeneity among these extended pedigrees, and ≈50% of families were linked to this region with the highest single-pedigree lod score being 3.6. We further restricted the linked region from 12.2 to 2.9 cM (2.37 Mb) by genotyping 15 additional markers in the 3 families with the highest lod scores. We sequenced 4 genes with a likely role in lipid metabolism as well as 2 genes residing directly under the linkage peak but found no evidence for a causative variant. None of the genes residing in the significantly restricted 2.37-Mb region has been associated previously with HDL-C metabolism. Conclusion - This study provides significant evidence for a gene influencing HDL-C on chromosome 4q31.21.

Original languageEnglish (US)
Pages (from-to)392-397
Number of pages6
JournalArteriosclerosis, thrombosis, and vascular biology
Volume26
Issue number2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Complex trait
  • Coronary heart disease
  • Family study
  • Gene identification
  • High-density lipoprotein cholesterol

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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