CETP variants cannot explain why Asian Indians have both the highest heart disease rates and lowest HDL cholesterol in Singapore (Clin Genet 2003)

The Singapore population comprises Chinese, Malays and Asian Indians. Within this population, Asian Indians have the highest rates of coronary heart disease, whereas Chinese have the lowest. Conversely, Indians have the lowest high-density lipoprotein cholesterol (HDL-C) concentrations, followed by Malays and Chinese. We studied the TaqIB and -629C>A polymorphisms at the CETP locus in 1300 Chinese, 364 Malay and 282 Asian Indian men, and in 1558 Chinese, 397 Malay and 306 Asian Indian women, to determine whether these polymorphisms are responsible for the ethnic difference in HDL-C concentration. The frequency of the B2 allele in Chinese, Malays and Indians was 0.384, 0.339 and 0.449 in men, and 0.379, 0.329 and 0.415 in women, respectively (p < 0.001). For the A-629 allele, the relative frequencies were 0.477, 0.423 and 0.592 in men and 0.486, 0.416 and 0.575 in women (p < 0.001). The two polymorphisms were in linkage disequilibrium (D / Dmax= 0.9772, p < 0.00001). The B2 and the A-629 alleles were associated with increased HDL-C concentrations in a dose-dependent manner. The B2 allele continued to show an association with HDL-C concentration, even after controlling for the genotype at position -629. Dietary cholesterol showed a significant interaction with the TaqIB polymorphism in determining HDL-C concentrations in Indians and Malays, but not in Chinese. In conclusion, the high frequencies of these polymorphisms in Asian Indians could not explain the observed ethnic differences in HDL-C concentration. Moreover, we observed an ethnic-specific interaction among dietary cholesterol, the TaqIB polymorphism and HDL-C concentrations.