Determination and use of haplotypes: Ethnic comparison and association of the lipoprotein lipase gene and coronary artery disease in Mexican-Americans

Purpose: To illustrate an approach of deriving haplotypes for genetic association studies, using the lipoprotein lipase (LPL) gene and coronary artery disease. Methods: Six polymorphisms sufficient to distinguish the most common haplotypes in the 3′ end of LPL were identified by genotyping 10 polymorphisms in a small pilot population. These were used to haplotype LPL in large family samples of Mexican-Americans and non-Hispanic Caucasians. A case-control association study was performed comparing Mexican-Americans with and without coronary artery disease. Results: The two ethnic groups exhibited significant genetic differences. Among Mexican-Americans, homozygosity for LPL haplotype 1 was protective against coronary artery disease (OR = 0.50, 95% CI 0.27–0.91). Conclusion: This study outlines the haplotype structure of the LPL gene, illustrates the utility of haplotype-based analysis in association studies, and demonstrates the importance of defining haplotype frequencies for different ethnic groups.