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ARS Home » Northeast Area » Boston, Massachusetts » Jean Mayer Human Nutrition Research Center On Aging » Research » Publications at this Location » Publication #145165
Title: THE TAQIB AND -629C>A POLYMORPHISMS AT THE CHOLESTEROL ESTER TRANSFER PROTEIN LOCUS. ASSOCIATIONS WITH LIPID LEVELS IN A MULTI-ETHNIC POPULATION. THE 1998 SINGAPORE NATIONAL HEALTH SURVEY

Author
item TAI, E SHYONG - SINGAPORE GENERAL HOSP
item ORDOVAS, JOSE - HNRCA
item CORELLA, DOLORES - HNRCA
item DEURENBERG-YAP, MABEL - SINGAPORE HLTH PROMO BORD
item ADICONIS, XIAN - HNRCA
item CHEW, S - SINGAPORE MINISTRY OFHLTH
item LOH, LI MING - SINGAPORE GENERAL HOSP
item TAN, CHEE ENG - SINGAPORE GENERAL HOSP

Submitted to: Clinical Genetics
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/4/2002
Publication Date: 1/1/2003
Citation: TAI, E., ORDOVAS, J.M., CORELLA, D., DEURENBERG-YAP, M., ADICONIS, X., CHEW, S.K., LOH, L., TAN, C. THE TAQIB AND -629C>A POLYMORPHISMS AT THE CHOLESTEROL ESTER TRANSFER PROTEIN LOCUS. ASSOCIATIONS WITH LIPID LEVELS IN A MULTI-ETHNIC POPULATION. THE 1998 SINGAPORE NATIONAL HEALTH SURVEY. Clinical Genetics. 2003;63:19-30.

Interpretive Summary: Very significant differences are observed in coronary heart disease among different ethnic groups. In the last few decades, there has been an alarming global increase in the incidence of this disease, especially among developing countries, probably due to sudden changes in lifestyle, including diet and physical activity. In order to examine these issues, we have studied different ethnic groups to see how they are affected by these modernization processes and how genetic factors and diet interacts to modulate their risk of disease. Specifically, we have studied a representative sample of the population of Singapore. This 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 HDL-C (good cholesterol) concentrations, followed by Malays and Chinese. We studied mutations in one of the genes involved in the metabolism of HDL, the CETP gene, to see if these mutations could explain the observed differences in risk or the responses to the modernization of lifestyle. Our data indicates that although these polymorphisms modulate the levels of HDL in blood, they do not explain the ethnic differences in disease. Moreover, we report an ethnic specific interaction between dietary cholesterol, mutations at this gene and HDL-C concentrations. These findings could help to establish preventive measures in these populations.

Technical Abstract: 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 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 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 were 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 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 so 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 between dietary cholesterol the TaqIB polymorphism and HDL-C concentrations.