|Lai, Chao Qiang|
|Tai, E Shyong - SINGAPORE GEN HOSPITAL|
|Tan, Chee Eng - SINGAPORE GEN HOSPITAL|
|Cutter, Jeffery - MINISTRY OF HEALTH|
|Chew, Suoki Kai - MINISTRY OF HEALTH|
|Zhu, Yue Ping - USDA-HNRCA|
|Adiconis, Xian - USDA-HNRCA|
|Ordvas, Jose - USDA-HNRCA|
Submitted to: Journal of Lipid Research
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 21, 2003
Publication Date: December 1, 2003
Citation: Lai, C., Tai, E., Tan, C., Cutter, J., Chew, S., Zhu, Y., Adiconis, X., Ordvas, J. 2003. The apolipoprotein a5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in singapore. Journal Of Lipid Research 2003;44:2365-73. Interpretive Summary: High level of triglycerides (TG) in blood is a risk factor for heart disease. The levels of TGs are determined by multiple factors including genes, diet and age. Therefore, a more precise determination of the relation between these factors will provide better tools to assess individual risk of heart disease as well as to prevent the clinical presentation of the disease using nutritional approaches. A new gene known as APOA5 has been recently discovered. This gene produces an apolipoprotein called (apo)A-V. This protein is associated with lipoproteins, the particles that carry fats in blood. Therefore, common genetic mutants may affect the characteristics of these lipoproteins resulting on elevated TG in blood. To investigate this hypothesis, we have investigated if common mutations at the APOA5 gene are associated with blood lipid levels in subjects for Chinese, Indian and Malay ancestry, for whom TG concentrations constitute a major risk for heart disease. We found very significant associations between four such common APOA5 mutations and higher blood TG concentrations across the three ethnic groups. Our data support the notion that the APOA5 gene is a major determinant of TG levels across ethnic boundaries, and contributes to potential risk factors for CHD for Chinese and Malays. We believe the findings of this work are of great interest to the scientific community and general public. These significant findings will be followed by research examining how this gene interacts with dietary factors and lifestyle to determine personal risk of heart disease in the USA population.
Technical Abstract: Singapore is a highly developed country comprising three major ethnic groups: Chinese (76.7%), Malays (14%) and Asian Indians (7.9%). Overall, Singaporeans suffer from high coronary heart disease (CHD) rates similar to those found in United States or Australia. However, there is a dramatic inter-ethnic gradient, with Asian Indians being at significantly higher risk than Chinese and Malays. These differences are mainly associated with high-density lipoprotein cholesterol levels that cannot be solely explained by environmental exposures, and that are probably driven by genetic factors. A new gene (APOA5) encoding for apolipoprotein (apo)A-V has been located next to the APOA1/APOC3/APOA4 gene cluster on chromosome 11. We investigated associations between common polymorphisms at the APOA5 locus and plasma lipid variables in 4,061 Singaporeans to establish whether this locus explained some of the ethnic differences in CHD risk. We found highly significant associations between the minor alleles at each one of four common polymorphisms and higher plasma triglyceride concentrations across the three ethnic groups. Haplotype analyses, using the 4 most common alleles, show significant associations with TG levels for all three ethnic groups, explaining 6.41% of the TG variance in Malays, 5.19% in Asian Indians, and 3.08% in Chinese. Conversely, we observed significant inverse associations between the minor alleles and HDL-C concentrations for Chinese and Malays. Our data support the notion that the APOA5 locus is a major determinant of TG levels across ethnic boundaries, and contributes to the variance of HDL-C concentrations for Chinese and Malays.