TNF-? gene polymorphisms in Type 1 (insulin-dependent) diabetes mellitus

Badenhoop, Klaus; Schwarz, G.; Trowsdale, John; Lewis, Victoria; Usadel, K. H.; Gale, E. A. M.; Bottazzo, Gian Franco

doi:10.1007/bf00271265

Cited by 61 publications

(32 citation statements)

References 10 publications

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“…allele with the disease. The gene frequencies are the same as in the control group and in agreement with the distribution described in previous reports [27,29,32,36]. Thus, no association can be found between PBC and the Nco\ RFLP.…”

Section: Discussionsupporting

confidence: 91%

“…The high frequency of HLA-B8 and HLA-DR3 antigens among patients with autoimmune diseases, and the tight linkage of the TNFB*1 allele with the B8-DR3 haplotype [27][28][29], has raised the possibility that variations of the TNF genes might be related to the individual disease susceptibilities. Thus, several groups have studied the association of the diallelic Nco\ RFLP indicative for the two TNF-/?…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Allelic Variation in the TNF‐β Gene Does Not Explain the Low TNF‐β Response in Patients With Primary Biliary Cirrhosis

Messer¹,

Spengler²,

Jung³

et al. 1991

Scand J Immunol

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Autoimmune disorders in humans are often associated with particular alleles of major histocompatibility genes. However, the chronic inflammatory liver disease primary biliary cirrhosis (PBC) has not been found to be correlated with certain haplotypes so far. Interestingly, an impaired production of tumour necrosis factor β (TNF‐β) upon mitogen stimulation was observed for PBC patients, especially in the immunologically active stages of the disease. Furthermore, the identification of alleles of the TNF‐β gene which differ in one unique amino acid, and in the production of TNF‐β after phytohaemagglutinin stimulation, has prompted the idea of a possible linkage between the impaired TNF‐β response in PBC and the genetic prevalence of a certain TNF haplotype. We report here a rapid method for typing the TNFB*1 and TNFB*2 genes by a standard polymerase chain reaction, PBC patients(n = 60)as well as randumized healthy controls (n = 179) of the Munich area were studied for the occurrence of the TNF alleles. No deviation was found in the PBC collective (0.7) for the TNFB*2 distribution when compared with the control (0.67).

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Allelic Variation in the TNF‐β Gene Does Not Explain the Low TNF‐β Response in Patients With Primary Biliary Cirrhosis

Messer¹,

Spengler²,

Jung³

et al. 1991

Scand J Immunol

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“…An extensive search for RFLP uncovered a diallelic NcoI RFLP [20,[36][37][38] and a rare diallelic EcoRI RFLP [39]. In spite of its limited informativity, analysis of the NcoI RFLP indicated some degree of association between TNF alleles and autoimmune diseases [20,36,37,40,411. We recently reported that the 10.5-kb NcoI allele (TNFB*2) correlates with increased TNF-a production from in vitro stimulated monocytes (Mo) from healthy individuals [20,42].…”

Section: Introductionmentioning

confidence: 99%

Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF‐a and TNF‐0 by human mononuclear cells: a possible link to insulin‐dependent diabetes mellitus

Pociot

Briant

Jongeneel³

et al. 1993

Eur J Immunol

542

354

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We have investigated the correlation between different tumor necrosis factor (TNF) and class II major histocompatibility complex alleles in the lipopolysaccharide- or phytohemagglutinin-induced secretion of TNF-alpha and TNF-beta by human monocytes and peripheral blood mononuclear cells in 87 unrelated Danish male individuals. Significant differences in TNF-alpha secretory capacity between TNF NcoI restriction fragment length polymorphisms, TNFa and TNFc microsatellite alleles and DR alleles were identified. No correlation with TNF-beta secretory capacity was found for any of the markers studied. TNF genotyping allowed us to define four extended HLA haplotypes which correlate with TNF-alpha secretory capacity. Two of these are DR4 positive: DQw8, DR4, TNFB*1, TNFa6, B44, A2 and DQw8, DR4, TNFB*2, TNFa2, B15, A2. Individuals carrying the TNFB*2, TNFa2 haplotype had a higher TNF-alpha secretory capacity than those carrying the TNFB*1, TNFa6 haplotype. In a group of DR3/DR4 heterozygous patients with insulin-dependent diabetes mellitus (IDDM), the frequency of the TNFa2 allele was higher than in HLA-DR matched controls, whereas the TNFa6 allele was more frequent in control individuals. In the DR3/DR4 heterozygous diabetic group 12/26 had the alleles combination DQw8, DR4 (Dw4), C4A3, TNFB*2, TNFa2, B15, whereas only 1/18 controls had this haplotype. This diabetogenic haplotype is identical to the DR4 haplotype which correlates with a higher TNF-alpha response. These observations suggest a direct role for the TNF locus in the pathogenesis of IDDM.

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“…Although several earlier studies [6,7] reported possible associations of tumour necrosis factor-fi (TNF-fi) and interleukin-lfi (IL-lfi) polymorphisms, this is, to our knowledge, the first description of association between IDDM and an IFN-y polymorphism. One should be cautious about the positive association, since multiple factors could give erroneous associations.…”

Section: Discussionmentioning

confidence: 68%

Association of polymorphism in the interferon g gene with IDDM

et al. 1994

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SummaryCytokines may play importmant roles in the pathogenesis of insulin-dependent diabetes mellitus (IDDM). We analysed a dinucleotide repeat polymorphism within the first intron of the interferon (IFN-v) gene in Japanese diabetic patients (175 IDDM and 145 non-insulin-dependent diabetes mellitus) and 267 control subjects. A significant difference was observed in the global allele distribution of the polymorphism between the IDDM and control groups (p = 0.039). The difference from the control group was more evident in the patients whose insulin therapy started within 1 year from onset (p = 0.006) or in the young-onset (< 10 years) patients (p = 0.0006). The alleles "3" and "6" were increased in the IDDM patients, and a significant increase in the frequency of the "3/6" genotype was observed in the IDDM patient group (9.1%, RR 2.9, p = 0.010), in the patients with initial insulin therapy less than 1year from onset (10.6%, RR 3.4, p = 0.004), or in the young-onset patients (16.7 %, RR 5.7, p = 0.0003) in comparison to the control subjects (3.4 %). There was a tendency towards frequent occurrence of clinical characteristics which reflect young or abrupt onset of diabetes or both, and depletion of insulin secretion capacity in the patients with "3/6" or "6/6" in comparison to the patients with other genotypes. These results suggest that the IFNgene region may contribute to the pathogenesis of IDDM and could be a genetic marker for IDDM. [Diabetologia (1994[Diabetologia ( ) 37: 1159[Diabetologia ( -1162 Key words Interferon gamma, gene, polymorphism, association, insulin dependent diabetes mellitus, susceptibility, Japanese.Abundant evidence suggests that insulin-dependent diabetes mellitus (IDDM) is caused by the destruction of pancreatic beta cells resulting from T lymphocyte-mediated autoimmune process. It is well established that the HLA class II region contributes to the development of IDDM. Furthermore, in Cauca-

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TNF-? gene polymorphisms in Type 1 (insulin-dependent) diabetes mellitus

Cited by 61 publications

References 10 publications

Allelic Variation in the TNF‐β Gene Does Not Explain the Low TNF‐β Response in Patients With Primary Biliary Cirrhosis

Allelic Variation in the TNF‐β Gene Does Not Explain the Low TNF‐β Response in Patients With Primary Biliary Cirrhosis

Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion of TNF‐a and TNF‐0 by human mononuclear cells: a possible link to insulin‐dependent diabetes mellitus

Association of polymorphism in the interferon g gene with IDDM

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