Background: Familial combined hyperlipidaemia (FCH) is the most common genetic dyslipidaemia associated with coronary artery disease. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A4/A5 gene cluster are associated with FCH in Caucasians and with elevated triglycerides (TG) in various ethnic groups. We examined these associations with FCH in Hong Kong Chinese.
Methods: Fifty-six Chinese FCH patients and 176 unrelated controls were studied. Thirteen SNPs in the APOA1/C3/A4/A5 cluster were genotyped.
Results: Four alleles in APOA5 were associated with FCH (P<0.001). The -1131T>C (rs662799) and -3A>G (rs651821) SNPs in APOA5 were in almost complete linkage disequilibrium (LD, r(2)=0.99), and their minor alleles were more frequent (P<0.001) in FCH than controls (0.60 vs. 0.24). The odds ratio (OR) for FCH was 6.2 (95% CI, 2.6-14.8) and 6.1 (2.6-14.6) per copy of -1131C and -3G, respectively, and 24.6 (8.4-72.0) and 24.4 (8.4-70.9) in -1131C and -3G homozygotes, respectively, as compared to wild-type homozygotes. The 1891T>C (rs2266788) SNP was in LD (r(2)=0.68) with -1131T>C and -3A>G, and the minor allele was more frequent in FCH than controls (0.42 vs. 0.19, P<0.001). The 553G>T (rs2075291) nonsynonymous variant was also associated with FCH (0.15 vs. 0.04, P=0.001) and, along with -3A>G (or -1131T>C) and 1891T>C, contributed to haplotypes predicting FCH. The two tightly linked SNPs, -1131T>C and -3A>G polymorphism were significantly associated with lipid traits in all subjects combined, with variant homozygous subjects having higher TG and LDL-C and lower HDL-C levels.
Conclusions: Some common polymorphisms and haplotypes in APOA5 are closely associated with FCH in Hong Kong Chinese, and these differ from those found in Caucasians.
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