title: Haplotype analysis finds linkage disequilibrium in the IL-12 gene in patients with HCV.
abstract: HCV is a major cause of liver disease worldwide. IL-12 plays an essential role in the balance of T helper 1 (Th1) differentiation versus a T helper 2 (Th2) driven response from its naïve precursor. Linkage disequilibrium measures the degree to which alleles at two loci are associated and the non-random associations between alleles at two loci. Haplotypes of the three IL-12B loci studied were determined in the patient cases and the normal healthy control subjects. The frequency of the 12 possible IL-12B haplotypes on the 3 loci was determined in subjects heterozygous at only one of the loci within the studied haplotype. Haplotype frequencies were compared between the patient groups and controls (n = 49) to determine if any preferential combination of markers occurred using chi-squared and applying the Bonferroni correction. 45 HCV RNA negative patients; 88 HCV RNA positive patients; and 15 uninfected cases at high risk of HCV infection (EU) were studied. The haplotype "C" SNP of the 3'UTR with the "E" 4 bp deletion of the intron 4 region was in linkage disequilibrium (χ(2)  = 45.15, P < 0.001, 95% CL). The haplotype analysis of the insertion allele of the promoter with the deletion allele of the intron 4("E") IL-12B polymorphism showed linkage disequilibrium (χ(2)  = 5.64, P = 0.02). Linkage disequilibrium of polymorphisms is reported in the IL-12 gene in patients with HCV infection and contributes to the understanding of patient genotype and expected production of IL-12, responding to infection.
authors.affiliation: Hepatology and Molecular Medicine Research Groups, Peninsula Medical School, Plymouth, United Kingdom.
authors.forename: Annwyne
authors.initials: A
authors.lastname: Houldsworth
authors.forename: Magdalena
authors.initials: M
authors.lastname: Metzner
authors.forename: Andrea
authors.initials: A
authors.lastname: Hodgkinson
authors.forename: Steve
authors.initials: S
authors.lastname: Shaw
authors.forename: Edward
authors.initials: E
authors.lastname: Kaminski
authors.forename: Andy G
authors.initials: AG
authors.lastname: Demaine
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Cramp
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D005260:Female; D005787:Gene Frequency; D006239:Haplotypes; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology; D006526:Hepatitis C / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D018664:Interleukin-12 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D020413:3' Untranslated Regions; D053762:Interleukin-12 Subunit p40; D018664:Interleukin-12
keywords: IL-12B gene; Proinflammatory cytokine; gene polymorphism; hepatitis C; virus clearance