Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients

Abstract

To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (> 13) or decreased (< 0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis.

The interferon gene cluster: a candidate region for MS predisposition?

“…After proteolytic cleavage of the signal peptide, the truncated protein would consist of only 30 aa. As proposed by Uzé et al 30 31 So far, the exact location of the intergenic microsatellite within the IFN region is not known. LD data obtained in this study provide evidence, that the (GT) n repetition is located centromeric, close to the IFNA17 gene.…”

Helicobacter pyloriInfection

“…Differences in allele or genotype distribution between the infected cohort and control cohort were quantitated using odds ratios (OR). Only 24 15.9 17.6 (GT) 23 9.7 7.7 (GT) 22 16.7 12.5 (GT) 21 7.7 6.3 (GT) 20 2.7 2.8 (GT) 19 0.0 0.3 (GT) 17 0.2 0.0 (GT) 16 0.5 2.0 (GT) 15 25.9 30.1 TCRBV6S3 alleles c (GT) 13 0.2 1.1 (GT) 12 10.3 9.2 (GT) 11 7.6 4.4 (GT) 10 0.0 0.0 (GT) 9 0.0 0.0 (GT) 8 81.9 85.3 TCRBV6S1 alleles c (GT) 13 11.8 8.6 (GT) 12 21.7 d 14.7 d (GT) 11 0.2 0.6 (GT) 10 0.5 0.0 (GT) 9 65. d OR ϭ 1.6; 2 ϭ 6.14; P ϭ 0.013; P c ϭ 0.04 (three alleles tested). e OR ϭ 0.6; 2 ϭ 9.6; P ϭ 0.0017; P c ϭ 0.005 (three alleles tested).…”

“…The distribution of the haplotypes TCRBV6S1/BV6S7 is shown in Table 5. The haplotype TCRBV6S1(GT) 12 /BV6S7(GT) 22 is significantly associated with H. pylori infection (OR ϭ 2.47; 2 ϭ 8.8; P ϭ 9 /BV6S3(GT) 8 was more frequent in uninfected controls, which could imply that a haplotype offers some protection from the disease. This haplotype, however, does not extend to the TCRBV6S7 element.…”

The Nonfunctional Allele TCRBV6S1B Is Strongly Associated withHelicobacter pyloriInfection

“…In the H. pylori-positive group, 40 individuals suffered from gastric ulcer or had a history of gastric ulcer and 40 individuals had developed duodenal ulcer. There was no evidence for acute ulceration or history of ulcer disease in 123 individuals.DNA preparation and microsatellite analysis were performed as described previously (8,11). Haplotype frequencies were estimated by using ARLEQUIN software (standard deviation computed by 50 bootstraps) (14).…”

“…DNA preparation and microsatellite analysis were performed as described previously (8,11). Haplotype frequencies were estimated by using ARLEQUIN software (standard deviation computed by 50 bootstraps) (14).…”