title: Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes.
abstract: We have studied 35 single nucleotide polymorphisms (SNPs) in the interferon (IFN) pathway to determine their contribution to multiple sclerosis (MS) and hepatitis C virus (HCV) infection. A total of 182 patients with MS, 103 patients with chronic hepatitis C, and 118 control subjects were enrolled in the study. Of the 35 SNPs studied, 3 were in IFN-alpha receptor (IFNAR-1), 10 in IFN-alpha/beta receptor (IFNAR-2), 9 in Stat1, 5 in Stat2, and 8 in IFN regulatory factor-1 (IRF-1). Compared to controls, Stat1 gene polymorphisms were significantly more frequent in MS patients (rs# 2066802 OR = 7.46, 95% CI = 2.22-25.10; rs# 1547550 OR = 1.69, 95% CI = 1.01-2.81) and in HCV patients (rs# 2066802 OR = 5.95, 95% CI = 1.55-22.81; rs# 1547550 OR = 2.30, 95% CI = 1.24-4.24). Also one IRF-1 gene SNP was associated with MS (rs# 2070721 OR = 2.05, 95% CI = 1.03-4.09), and four IRF-1 gene SNPs were associated with HCV infection (rs# 2070721 OR = 2.59, 95% CI = 1.23-5.43; rs# 2070723 OR = 4.8, 95% CI = 1.26-18.20; rs# 2070728 OR = 9.81, 95% CI = 1.21-79.4; rs# 2070729 OR = 3.6, 95% CI = 1.23-10.48; rs# 839 OR = 4.67, 95%CI = 1.29-16.87). Characteristic nucleotide combinations on single chromosomes (haplotype) generated block structures, including SNPs, that differed between patients and controls. Using a permutation test to detect differences in haplotype distribution between groups, the CCATTGA and the CCGAA haplotypes in the IRF-1 gene were more frequent in MS (p = 0.03) and in HCV patients (p = 0.001) than in controls. In conclusion, our data show that genetic variants in the IRF-1 and Stat1 genes of the IFN pathway are associated with MS and HCV infection.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Fortunato
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Calcagno
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bresciamorra
authors.forename: Elena
authors.initials: E
authors.lastname: Salvatore
authors.forename: Alessandro
authors.initials: A
authors.lastname: Filla
authors.forename: Silvana
authors.initials: S
authors.lastname: Capone
authors.forename: Rosario
authors.initials: R
authors.lastname: Liguori
authors.forename: Salvatore
authors.initials: S
authors.lastname: Borelli
authors.forename: Ivan
authors.initials: I
authors.lastname: Gentile
authors.forename: Francesco
authors.initials: F
authors.lastname: Borrelli
authors.forename: Guglielmo
authors.initials: G
authors.lastname: Borgia
authors.forename: Lucia
authors.initials: L
authors.lastname: Sacchetti
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology / Q000821:virology; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics*; D007372:Interferons / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D053633:Receptor, Interferon alpha-beta / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000235:genetics*; D050799:STAT5 Transcription Factor / Q000235:genetics; D015398:Signal Transduction
chemical_list: C507964:IFNAR1 protein, human; C508033:IFNAR2 protein, human; D050856:Interferon Regulatory Factor-1; D050794:STAT1 Transcription Factor; C494079:STAT1 protein, human; D050799:STAT5 Transcription Factor; D053633:Receptor, Interferon alpha-beta; D007372:Interferons