ASSOCIATION OF LIPOPROTEIN-LIPASE GENE VARIATION WITH THE PHYSIOLOGICAL COMPONENTS OF THE INSULIN-RESISTANCE SYNDROME IN THE POPULATION OF THE SAN-LUIS-VALLEY, COLORADO

OBJECTIVE- To cross-sectionally evaluate the presence of clustering of the insulin-resistance syndrome components. Tests were conducted for association of the HindIII restriction site polymorphism at the lipoprotein lipase locus with clustering of the physiological components of the insulin resistance syndrome. RESEARCH DESIGN AND METHODS- DNA samples of 370 normoglycemic Hispanics and 520 normoglycemic non-Hispanic whites from the San Luis Valley, Colorado, were amplified by the polymerase chain reaction. lipids and glucose were determined by the standard procedures. Cross-tabulation and chi2 analysis were used. RESULTS - The insulin-resistance syndrome components (elevated fasting insulin, reduced high-density lipoprotein cholesterol, and elevated triglycerides) appeared together in individuals of this population sample more often than expected by chance. Individuals in the population with the (+/+) lipoprotein lipase-HindIII restriction of fragment-length polymorphism genotype were more likely to have elevated fasting insulin and triglycerides and a reduced high-density lipoprotein-cholesterol level than subjects with the (+/-) genotype (odds ratio = 2.3, 95% confidence interval 1.38-3.98). CONCLUSIONS- As expected from the physiological function of lipoprotein lipase, the primary association of lipoprotein lipase genotypes is with triglyceride and high-density lipoprotein-cholesterol levels. This appears to be the first reported genetic association with the insulin-resistance syndrome and may reflect genotype specific differences in the regulation of lipoprotein lipase by insulin.