|Paik, Jean Kyung|
|Hyun, Yae Jung|
|Chae, Jey Sook|
|Kim, Ji Young|
|Choi, Ju Ree|
|Lee, Sang Hak|
|Lee, Jong Ho|
Submitted to: Clinica Chimica Acta
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/17/2008
Publication Date: 4/1/2009
Citation: Jang, Y., Paik, J., Hyun, Y., Chae, J., Kim, J., Choi, J., Lee, S., Shin, D., Ordovas, J., Lee, J. 2009. The apolipoprotein A5 -1131T>C promoter polymorphism in Koreans: association with plasma APOA5 and serum triglyceride concentrations, LDL particle size and coronary artery disease. Clinica Chimica Acta. 402(1-2):83-87. Interpretive Summary: Cardiovascular diseases are the major cause of death and disability in industrialized countries and a major barrier to healthy aging. Cardiovascular diseases are the result of the interaction between a number of genetic and environmental risk factors, being blood lipid concentrations (i.e., cholesterol and triglycerides) among the best studied and known. Apolipoprotein A5 (APOA5) is known to play a major role in triglyceride metabolism. A major translational goal of genetic research involves the identification of genetic variants that could predict disease susceptibility before disease strikes. Whereas there are many reports showing relations between genetic polymorphisms and disease risk factors, the final objective is to identify polymorphisms that predict disease. In this regard, the relation between polymorphisms at a gene coding for a protein present in blood lipoproteins, known as apolipoprotein A5 (APOA5) and triglycerides (TG) levels is well established. However, the associations between apoA5 concentrations, TG and coronary artery disease (CAD) remain controversial. We investigated these relations in the setting of a case (n=367)-control (n=777) study involving Korean males. We examined the association between a polymorphism in the regulatory region of the APOA5 gene known as -1131T>C, high triglycerides and coronary artery disease (CAD) risk. Our data show that the presence of the genetic variant was associated with an increased risk of CAD, higher blood triglyceride and smaller LDL particle size, another risk factor for CAD. In conclusion, the APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. Consistent with the observed association between the gene variant and increased triglycerides as well as small LDL particle size. Therefore, APOA5 polymorphisms could be used for early identification of those at high risk for CHD and successful prevention of age related diseases.
Technical Abstract: BACKGROUND: The association between -1131T>C single nucleotide polymorphism (SNP) of the apolipoprotein A5 gene (APOA5) and hypertriglyceridemia raised the possibility that this SNP could be related to coronary artery disease (CAD) risk. Therefore, we investigated the association of this APOA5 -1131T>C SNP with circulating concentrations of APOA5, triglyceride and CAD in Koreans. METHODS: CAD patients (n=741) and age-, sex-matched healthy controls (n=741) were genotyped for the APOA5 -1131T>C SNP. The main outcome measures were the odds ratio (OR) on CAD risk and lipid variables, APOA5 concentration and LDL particle size. RESULTS: The presence of the minor allele at the -1131T>C SNP was associated with an increased risk of CAD [OR 1.34 (95% CI, 1.09-1.65), P=0.007] after adjusting for BMI, alcohol consumption, systolic blood pressure and diastolic blood pressure. There was an association between the APOA5 concentration and the -1131T>C genotype in controls (T/T: 245+/-7 ng/ml, T/C: 220+/-6, C/C: 195+/-12; P=0.001) and CAD patients (T/T: 218+/-8 ng/ml, T/C: 185+/-7, C/C: 169+/-12; P<0.001). Subjects with T/C or C/C in control and CAD patient groups showed higher triglyceride than those with T/T genotype. Also, the -1131T>C polymorphism was associated with LDL particle size (P=0.003), with the T/C or C/C controls having smaller size than the T/T controls. CONCLUSIONS: The APOA5 -1131C allele is associated with reduced APOA5 concentration and with increased CAD risk. This is consistent with the observed association between the -1131C SNP, increased triglycerides as well as small LDL particle size.