title: Association of single nucleotide polymorphisms of the interleukin-10 promoter gene and susceptibility to primary biliary cirrhosis: immunogenetic differences in Italian and Japanese patients.
abstract: Several lines of data suggest that genetic factors play an important role in the onset and/or progression of primary biliary cirrhosis (PBC). Since PBC is an autoimmune disease, it is reasoned to assume that genes encoding cytokines may confer susceptibility to disease. Amongst these factors, interleukin-10 (IL-10) has received significant attention. The promoter region of IL-10 gene has three single nucleotide polymorphisms (SNPs) at positions -1082, -819 and -592. To elucidate the association of the three SNPs of IL-10 promoter region with susceptibility of PBC in two different genetic populations, 159 unrelated patients with PBC (94 Italian and 65 Japanese) and 143 local controls (72 Italian and 71 Japanese) were enrolled. SNPs were determined using allele-specific PCR/RFLP. In Italian PBC patients, the frequency of homozygosity for G/G at position -1082 was significantly higher than that of local controls (p < 0.041, OR = 2.44, 95% C.I.; 1.02-5.86). The frequencies of haplotype GCC in PBC patients, possibly linked to higher IL-10 production, were also significant higher than local controls (p < 0.033). However, in Japanese population, there were no significant differences in the three SNPs and haplotypes between PBC patients and controls. Excessive production of IL-10 may play an important role in some populations in modulating the onset of PBC. Further, immunogenetic studies of PBC should take into account ethnic and geographic variations; this makes such studies in heterogeneous population, like the USA, more difficult.
authors.affiliation: Fourth Department of Internal Medicine, Teikyo University School of Medicine, Kanagawa 213-8507, Japan.
authors.forename: Masanao
authors.initials: M
authors.lastname: Matsushita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kikuchi
authors.forename: Eriko
authors.initials: E
authors.lastname: Kitazawa
authors.forename: Naomi
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Takashi
authors.initials: T
authors.lastname: Kato
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Fujikawa
authors.forename: Stefano
authors.initials: S
authors.lastname: Quaranta
authors.forename: Floriano
authors.initials: F
authors.lastname: Rosina
authors.forename: M Eric
authors.initials: ME
authors.lastname: Gershwind
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Miyakawa
mesh_terms: D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D016753:Interleukin-10 / Q000235:genetics*; D007558:Italy; D007564:Japan; D008105:Liver Cirrhosis, Biliary / Q000235:genetics* / Q000276:immunology; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
chemical_list: D016753:Interleukin-10