SNPs at the APOA5 gene account for the strong association with hypertriglyceridaemia at the APOA5/A4/C3/A1 locus on chromosome 11q23 in the Northern Irish population.
Serum triglyceride levels (TG) are important independent risk factors for coronary heart disease. The apolipoproteins C-III (apoCIII) and A-V (apoAV) are central to normal TG metabolism and the complete sequence analysis of these genes was carried out in severe cases (TG > 9 mmol/l) and controls (TG < 2 mmol/l). A total of 53 SNPs were identified in these genes with 17 being novel to this study. Further analysis defined four APOC3 SNPs and three APOA5 SNPs showing strong association with TG levels. Analysis of the two major SNPs from APOA5 [c.56C > G, c.-3A > G] and from APOC3 [c.102C > T, c.340C > G] using THESIAS has identified two major haplotypes relative to the most common CACC haplotype showing very strong association with hypertriglyceridaemia, CGTG and GATC (odds ratio 7.45 and 5.26). Logistic regression analysis of these four SNPs revealed that, carriage of the APOA5 c.56 G allele (odd ratios 4.49) and the APOA5 c.-3 G allele (odds ratio 3.23) were strong independent predictors of hypertriglyceridaemia (P < 0.001), whereas in contrast, carriage of the APOC3 c102 T allele (odds ratio 1.35) and the APOC3 c.340 G allele (odds ratio 1.37), did not show any significant effects that were independent of APOA5.
Wright
William T
WT
Centre for Clinical and Population Science, Queen's University, Belfast BT9 7AB, UK.
Young
Ian S
IS
Nicholls
D Paul
DP
Patterson
Chris
C
Lyttle
Kelly
K
Graham
Colin A
CA
D016632:Apolipoprotein A-I / Q000235:genetics; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins / Q000235:genetics*; D001054:Apolipoproteins A / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D002880:Chromosomes, Human, Pair 11; D005260:Female; D005823:Genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015228:Hypertriglyceridemia / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood
C505693:APOA1 protein, human; C437704:APOA5 protein, human; D016632:Apolipoprotein A-I; D000072040:Apolipoprotein A-V; D053305:Apolipoprotein C-III; D001053:Apolipoproteins; D001054:Apolipoproteins A; D001056:Apolipoproteins C; D014280:Triglycerides; C022205:apolipoprotein A-IV