Apolipoprotein A5 gene IVS3+G476A allelic variant confers susceptibility for development of ischemic stroke.
BACKGROUND
T-1131C, T1259C and IVS3+G476A are naturally occurring variants of the apolipoprotein A5 (APOA5) gene and their possible impact on the development of ischemic stroke was investigated in the present study.


RESULTS
PCR-RFLP assays were used to determine the distributions of the APOA5 alleles in small-vessel, large-vessel and mixed subgroups of 378 patients and in 131 stroke-free control subjects. Increased triglyceride levels were found in subjects carrying -1131C, 1259C, IVS3+476A alleles in all stroke groups and in the controls. The -1131C and IVS3+476A alleles, but not the T1259C variant, showed significant accumulation in all stroke subgroups. Logistic regression analysis adjusted for age, gender, body mass index, total cholesterol level, ischemic heart disease, hypertension, diabetes mellitus, smoking-and drinking habits revealed that the IVS3+476A allele represents independent susceptibility factor for stroke (odds ratio for small-vessel: 4.748; large-vessel: 3.905; mixed: 2.926; overall: 3.644 at 95% confidence interval; p<0.05), we could also confirm the previously verified pathogenic role of the -1131C variant.


CONCLUSIONS
All of the 3 APOA5 variants are associated with elevated triglycerides, but only the -1131C and the IVS3+476A alleles confer risk for all types of ischemic stroke; such an association could not be detected for the 1259C allele.
Maasz
Anita
A
University of Pecs, Department of Medical Genetics and Child Development, Pecs, Szigeti 12, H-7624, Hungary. anita.maasz@aok.pte.hu
Kisfali
Peter
P
Jaromi
Luca
L
Horvatovich
Katalin
K
Szolnoki
Zoltan
Z
Csongei
Veronika
V
Safrany
Eniko
E
Sipeky
Csilla
C
Hadarits
Ferenc
F
Melegh
Bela
B
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D002545:Brain Ischemia / Q000453:epidemiology* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012044:Regression Analysis; D012307:Risk Factors; D020521:Stroke / Q000453:epidemiology* / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D014280:Triglycerides; D002784:Cholesterol