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TWO GENETIC VARIATIONS OF APOLIPOPROTEIN A-1 WERE ASSOCIATED WITH HDL-C AND APOA-1 LEVEL IN A HELTHY KOREAN POPULATION.
연세대학교 의과대학 심장혈관병원 심혈관 연구소¹ ,심장내과²
문재연¹ ², 서혜선¹ ² , 고영국¹ ² , 강석민¹ ² , 정남식¹ ² , 심원흠¹ ² , 조승연¹ ² , 조은영 ¹ , 이종호¹ , 이종은¹ , 박현영¹ ², 장양수 ¹ ²
Background: Previous studies showed that two polymorphisms of Apo-A1, G-75A and XmnI restriction site confers increased plasma high-density lipoprotein cholesterol (HDL-C) and triglyceride in Caucasians, respectively. In this study, we investigated the role of two polymorphisms of apoA-1 gene in lipid profiles and serum apo-A1 level in healthy Korean subjects. Method: We obtained blood samples from unrelated 417 consecutive subjects (M: F=169:248, mean age 47.2 years) without any history or clinical signs of CAD, diabetes and hypertension. The apo-A1 genotypes were determined by SNP-ITTM assays using SNPstream 25KTM System. The plasma apoA-1 level was determined by immunoturbidometric analyzer. Result: The genotype frequencies of G-75A(MspI restriction site) were 69%, 26%, and 5% for GG, GA and AA, respectively. The genotype frequencies for XmnI restriction site were 57%, 39%, and 4% for GG, GA and AA respectively. It was previously reported that the A allele frequency at XmnI restriction site was about 12-14% in Caucasian. The A allele frequency at XmnI restriction site in our study population was higher (23.5%) than that of Caucasian. The A allele at ?5 locus was also associated with higher plasma HDL-C levels (p=0.040) and the A allele at XmnI restriction site was significantly associated with lower triglyceride levels (p=0.009) and higher ApoA-1 levels (p=0.049). Subjects carrying GG genotype at -75 locus and GG genotype at XmnI restriction site (GG/GG) showed significant higher triglyceride levels and lower apoA-1 levels compared to the other diplotypes(GG/GA, GA/GA, AA/AA). Significant linkage disequilibrium between two genetic variations was detected (p<0.001). Conclusion: The genotype variants of G-75A polymorphism with A allele in apoA-1 gene were associated with elevated HDL-C levels. These two variants of apoA-1 gene had strong linkage disequilibrium in Koreans. In contrast to previous reports, our study showed that the A variation at XmnI restriction site was also associated with decreased triglyceride and elevated apoA-1 levels, suggesting protective effects of A allele.


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