Microsatellite polymorphism within the MICB gene among japanese patients with behçet’s disease

Kimura, Tamon; Goto, Kaori; Yabuki, Kazuro; Mizuki, Nobuhisa; Tamiya, Gen; Kimura, Minoru; Inoko, Hidetoshi; Ohno, Shigeaki

doi:10.1016/s0198-8859(98)00047-0

Cited by 34 publications

(37 citation statements)

References 10 publications

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“…In this respect, the absence of linkage disequilibrium with HLA class II haplotypes and with TNFA alleles is highly relevant. These results are in line with the absence of linkage disequilibrium between the MIC-A and the MIC-B genes [43,44], that we have also confirmed in the Italian cohort [30], and this is presumably due to a recombination hot-spot between the two MIC genes [45]. The results of our paper are thus consistent with the hypothesis that the association of MIC-A polymorphism with Type I diabetes is not due to a linkage disequilibrium with genes located centromeric to the MIC-A gene, e. g. in the HLA class II and class III regions.…”

Section: Discussionsupporting

confidence: 82%

Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes

et al. 2000

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Type I (insulin-dependent) diabetes mellitus is an autoimmune disease characterised by the presence of circulating islet autoantibodies and by T-lymphocyte infiltration of the islets of Langerhans with consequent destruction of pancreatic beta cells [1]. A permissive genetic background is required for the development of the islet autoimmune process. Type I diabetes is a complex genetic disease and a long series of genes has been found to be linked with disease Diabetologia (2000) Methods. Type I diabetic (n = 95) and healthy (n = 98) Italian subjects were typed for exon 5 of MIC-A and for HLA-DRB1, HLA-DQA1, HLA-DQB1 and TNFA alleles. All subjects were also typed for the presence of HLA-B8 or HLA-B15.Results. The frequency of MIC-A5 was increased in diabetic subjects (53 % vs 15 %) (OR = 6.1) (corrected p, p c < 0.0005). Among HLA class II haplotypes, both HLA-DRB1*03-DQA1*0501-DQB1*0201 (DR3-DQ2) and DRB1*04-DQA1*0301-DQB1*0302 (DR4-DQ8) (ªat-risk class II haplotypesº) were positively associated with diabetes (OR = 6.7 and 6.0, respectively) (p c < 0.003). Also HLA-B8 was more frequent among Type I diabetic subjects than among healthy control subjects (OR = 2.8, p = 0.01). None of the TNFA alleles were statistically significantly associated with Type I diabetes. The MIC-A5 exon was negatively associated with age at clinical onset of diabetes (p = 0.012). Thus, 68 % diabetic subjects younger than 25 years and 29 % older than 25 years were carrying this allele. Both MIC-A5 and the at-risk class II haplotypes were independently associated with Type I diabetes and the combined association of the two markers had the highest relative risk (OR = 172). In subjects younger than 25 years, the OR of MIC-A5 was as high as 21.7 and was more than twofold that of at-risk class II haplotypes (OR = 9.5). The MIC-A5 exon was not in linkage disequilibrium with any of the HLA-class I, class II or TNFA alleles studied. Conclusions/interpretation. The MIC-A gene polymorphism is associated with genetic risk for Type I diabetes and the combination of MIC-A5 and at-risk class II haplotypes is now to be seen as the strongest genetic marker for this disease. [Diabetologia (2000) 43: 507±514]

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Section: Discussionsupporting

confidence: 82%

Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes

et al. 2000

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“…33 This MICA microsatellite can therefore be used to assess a possible association of several MICA alleles to disease. Regarding the MICB microsatellite in intron 1, 29 information about linkage to MICB exon polymorphisms is not available. However, the observed linkage disequilibrium between the MICB24 marker and B8, MICA5.1, and DR3 in the present study supports the notion that the MICB microsatellite is also useful to detect a possible association of MICB exon polymorphisms to disease.…”

Section: Discussionmentioning

confidence: 99%

“…28 A GT dinucleotide repeat in intron 1 of the MICB gene was amplified with PCR primers spanning 221 to 253 bp (MICB5F: 5Ј CTC CTT GCC AAA CTT GCT GT 3Ј; MICB5R: 5Ј ATG AGA AGC TAT GTG GGG GAG 3Ј). 29 PCR products were separated on a 4.25% urea-polyacrylamide gel and identified according to size on an ABI 377XL DNA sequencer. The alleles at each microsatellite were named according to the number of repeats they contained, i.e., MICA4 contains 4 GCT repeats and MICB24 contains 24 GT repeats.…”

Section: Patients Andmentioning

confidence: 99%

Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype including particular MICA and MICB alleles

WIENCKE¹,

SPURKLAND²,

SCHRUMPF³

et al. 2001

Hepatology

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Susceptibility to primary sclerosing cholangitis (PSC) is associated with HLA-B8, -DR3, -DR2, and -DR6. It is not established whether these HLA genes or closely linked genes confer the primary disease susceptibility. MICA and MICB genes are found in the class I region between HLA-B and DRB. MICA is expressed in gastrointestinal epithelium and activates ␥␦ T cells in the gut. Because PSC is strongly associated with inflammatory bowel disease, we investigated whether MICA and MICB contribute to the HLA-associated genetic susceptibility to develop PSC. The study included 130 PSC patients and 306 healthy controls, previously typed for HLA class I and II genes, typed for 5 MICA and 15 MICB microsatellite alleles. The phenotype frequencies of MICA5.1 and MICB24 were significantly increased among PSC patients compared with controls (90% vs. 74%; odds ratio [OR] ‫؍‬ 3.2; P c ‫؍‬ 3 ؋ 10 ؊3 and 58% vs. 29%; OR ‫؍‬ 3.3; P c < 1 ؋ 10 ؊7 , respectively). When stratified for B8-or DR3-positive and -negative individuals, the association of these markers to PSC was no longer evident. However, we observed that B8 and DR3 were associated to PSC only in the presence of both MICA5.1 and MICB24 markers. The frequency of individuals carrying all 4 alleles was significantly increased among the PSC patients compared with controls (49% vs. 18%; OR ‫؍‬ 4.5; P c < 1 ؋ 10 ؊7 ). Our data indicate that PSC is associated to the extended B8-MICA5.1-MICB24-DR3 haplotype. (HEPATOLOGY 2001;34:625-630.)Primary sclerosing cholangitis (PSC) is a chronic liver disease characterized by inflammatory and fibrotic bile duct lesions forming multiple strictures and ectatic dilatations of the intra-and extrahepatic bile ducts.

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“…100,101 Some cases have been associated with the MHC class I chain-related molecule A gene located near the B51 gene. 102 Heat shock proteins (HSP) are elevated in BD and have been found to upregulate the expression of the MHC class I chain-related molecule A locus. The human HSP60 has been capable of inducing uveitis in rats, 103 in Japanese patients with BD, 104 and in Turkish patients with BD 105 with increased T cell proliferation to HSP antigens detected in association with increased mRNA for IL-8, TNF-α and TNF-β.…”

Section: Behçet's Diseasementioning

confidence: 99%

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

Ooi¹,

Galatowicz²,

Calder³

et al. 2006

Clinical Medicine & Research

133

118

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Microsatellite polymorphism within the MICB gene among japanese patients with behçet’s disease

Cited by 34 publications

References 10 publications

Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes

Association of MHC Class I chain-related A (MIC-A) gene polymorphism with Type I diabetes

Primary sclerosing cholangitis is associated to an extended B8-DR3 haplotype including particular MICA and MICB alleles

Cytokines and Chemokines in Uveitis - Is there a Correlation with Clinical Phenotype?

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