Multiple sclerosis and hepatitis C virus infection are associated with single nucleotide polymorphisms in interferon pathway genes.
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.
Fortunato
Giuliana
G
Dipartimento di Biochimica e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Napoli, Italy.
Calcagno
Giuseppe
G
Bresciamorra
Vincenzo
V
Salvatore
Elena
E
Filla
Alessandro
A
Capone
Silvana
S
Liguori
Rosario
R
Borelli
Salvatore
S
Gentile
Ivan
I
Borrelli
Francesco
F
Borgia
Guglielmo
G
Sacchetti
Lucia
L
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
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