Associations of polymorphisms in the apolipoprotein A1/C3/A4/A5 gene cluster with familial combined hyperlipidaemia in Hong Kong Chinese.
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.
Liu
Zhi-Kai
ZK
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
Hu
Miao
M
Baum
Larry
L
Thomas
G Neil
GN
Tomlinson
Brian
B
D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics*; D044466:Asian People; D002681:China; D005260:Female; D006239:Haplotypes; D006723:Hong Kong; D006801:Humans; D006949:Hyperlipidemias / Q000208:ethnology* / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D005810:Multigene Family; D010641:Phenotype; D011110:Polymorphism, Genetic
C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001054:Apolipoproteins A; C022205:apolipoprotein A-IV