title: Haplotype analysis of the apolipoprotein A5 gene in patients with the metabolic syndrome.
abstract: OBJECTIVE
  In recent studies, the T-1131C variant of apolipoprotein A5 (APOA5) gene was found to confer a risk for metabolic syndrome (MS). Here we determined four haplotype-tagging polymorphisms (T-1131C, IVS3+G476A, T1259C, and C56G), and studied the distribution of the naturally occurring major haplotype profiles in MS.
  
  
  RESULTS
  A total of 343 MS patients and 284 controls were genotyped using PCR-RFLP methods. Both in MS and control groups, we confirmed the already known association of -1131C, IVS3+473A and 1259C minor alleles with elevated triglyceride levels. The prevalence of the APOA5*2 haplotype (the combination of T-1131C, IVS3+G476A and T1259C SNPs) was 13.1% in MS patients, and 4.9% in controls (p<0.001); multiple logistic regression analysis revealed that this haplotype confers risk for the development of MS (OR=2.880; 95% CI: 1.567-5.292; p=0.001). We also observed a gender effect: in males a more prominent degree of susceptibility was found. Contrary to the APOA5*2 haplotype, the prevalence rate of APOA5*4 (determined by the T-1131C SNP alone) did not differ between MS patients and controls. We identified a novel haplotype, designated here as APOA5*5 (1259C allele alone); which appears to be protective against MS.
  
  
  CONCLUSIONS
  Our results refined the role of SNP T-1131C in the development of MS. The susceptibility nature of this SNP is limited to the APOA5*2 haplotype, while in APOA5*4 haplotype it did not confer a risk for the disease. In addition, as our current data suggest, the novel APOA5*5 haplotype can confer protection against MS.
authors.affiliation: Department of Medical Genetics and Child Development, University of Pécs, Pécs, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Kisfali
authors.forename: M
authors.initials: M
authors.lastname: Mohás
authors.forename: A
authors.initials: A
authors.lastname: Maász
authors.forename: N
authors.initials: N
authors.lastname: Polgár
authors.forename: F
authors.initials: F
authors.lastname: Hadarits
authors.forename: L
authors.initials: L
authors.lastname: Markó
authors.forename: P
authors.initials: P
authors.lastname: Brasnyó
authors.forename: K
authors.initials: K
authors.lastname: Horvatovich
authors.forename: T
authors.initials: T
authors.lastname: Oroszlán
authors.forename: Z
authors.initials: Z
authors.lastname: Bagosi
authors.forename: Z
authors.initials: Z
authors.lastname: Bujtor
authors.forename: B
authors.initials: B
authors.lastname: Gasztonyi
authors.forename: J
authors.initials: J
authors.lastname: Rinfel
authors.forename: I
authors.initials: I
authors.lastname: Wittmann
authors.forename: B
authors.initials: B
authors.lastname: Melegh
mesh_terms: D000328:Adult; D000368:Aged; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D006814:Hungary; D016015:Logistic Models; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018570:Risk Assessment; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood; D015854:Up-Regulation; D055815:Young Adult
chemical_list: C437704:APOA5 protein, human; D000072040:Apolipoprotein A-V; D001054:Apolipoproteins A; D015415:Biomarkers; D014280:Triglycerides