title: TNF-alpha-308G>A polymorphism and the risk of familial CAD in a Pakistani population.
abstract: A case-control and trio-families study was performed to establish a potential association between TNF-alpha gene promoter SNPs at -308 and -238, and occurrence of CAD in a Pakistani population. In the first phase, 150 patients and 150 controls were enrolled in the case-control association study. In the second phase, heritability of susceptible alleles was investigated from 88 trio-families with CAD affected offspring. Biochemical analysis of lipids and hs-CRP was carried out spectrophotometrically, while serum TNF-alpha concentrations were determined by enzyme-linked immunosorbent assay. Genotyping of the TNF-alpha SNPs were determined by PCR-RFLP method. Elevated serum TNF-alpha and hs-CRP were observed from CAD vs. controls (P<0.0001; for both). The evaluation of TNF-alpha-308G>A polymorphism in case-control study revealed that the said SNP was significantly associated with the increased risk of CAD. The findings demonstrated a significant link between the TNF-alpha variant allele A at -308 and CAD (P=0.0035), whereas the -238 SNP was not associated with the disease. Haplotype A-G of the TNF-alpha gene at -308G>A and -238G>A showed higher frequency in the patient group compared with controls (P<0.05). Moreover, data showed preferential transmission of the disease susceptible allele A at TNF-alpha-308 from parent to affected offspring in a trio-family study (P<0.0001). The current research leads to conclusion that the TNF-alpha-308G>A polymorphism is associated with CAD in the study population. Furthermore, for the first time, we showed that the TNF-alpha-308A allele was significantly associated with the familial CAD in our high risk population.
authors.affiliation: Department of Biosciences, COMSATS Institute of Information Technology, Park Road, Chak Shazad, Islamabad 44000, Pakistan. Electronic address: spolymerase5@gmail.com.
authors.forename: Sabir
authors.initials: S
authors.lastname: Hussain
authors.affiliation: Department of Internal Medicine, Shifa College of Medicine, Shifa International Hospital, H-8/4, Islamabad 44000, Pakistan.
authors.forename: Tahir
authors.initials: T
authors.lastname: Iqbal
authors.affiliation: Department of Biochemistry, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan.
authors.forename: Qamar
authors.initials: Q
authors.lastname: Javed
mesh_terms: D000328:Adult; D000483:Alleles; D002097:C-Reactive Protein / Q000276:immunology / Q000378:metabolism; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010154:Pakistan; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D012306:Risk; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics* / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein
keywords: Association; Familial CAD; Polymorphism; TDT; TNF-alpha