HLA‐A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin‐dependent diabetes mellitus (IDDM)

Mouzon, A. Cambon-De; Ohayon, E; Hauptmann, G.; Sevin, A.; Abbal, M.; Sommer, E.; Vergnes, Hugues; Ducos, J

doi:10.1111/j.1399-0039.1982.tb01463.x

Cited by 55 publications

(9 citation statements)

References 2 publications

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“…The frequency of homozygous null C4B phenotypes was reported to be increased in patients with IgA nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN) [1], The high frequency of partial complement 4 (C4) defi ciency was also reported in patients with such autoimmune diseases as systemic lupus erythematosus [2][3][4], insulin-de pendent diabetes mellitus [5][6][7] and Graves' disease [8], Two extended hyplotypes, HLA-A1, Cw7, B8, C4AQ0, C4BI, Accepted : October 23.1992 DR3 and HLA-A30, Cw5. B18, C4A3, C4BQ0, DR3, are known to be associated with such autoimmune diseases, and there has been a debate about the relative importance between the C4 null alleles and the HLA antigens in the pathogenesis of the diseases.…”

Section: Introductionmentioning

confidence: 99%

Genetic Study on HLA Class II and Class III Region in the Disease Associated with IgA Nephropathy

Abe¹,

Kohsaka

Tanaka³

et al. 1993

Nephron

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Increased frequency of C4 gene deletions in IgA nephropathy and Henoch-Schönlein purpura nephritis. To determine the frequency of complement 4 (C4) deficiency among the patients with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN), C4 and factor B protein allotypes and the DNA restriction fragment length polymorphism (RFLP) of C4, steroid 21-hydroxylase (210Hase), HLA DQβ and DRβ chain genes were studied. Genomic DNA from 32 patients with IgAN, 24 patients with HSPN and 143 controls was digested with restriction enzyme TaqI or BamHI and subjected to Southern analysis. The frequency of C4 gene deletions was significantly increased in the patients (16.1 vs. 2.8%, p = 0.002). The serum C4 concentration in patients with C4 gene deletion was significantly lower than in patients without gene deletion (11.4 ± 2.4 vs. 19.7 ± 5.2 mg/dl, p = 0.001). DNA-RFLP typing of DQB/BamHI and DRB/ TaqI showed increased frequency of 10.26 kb of D-DQw4/8/9 (87.5 vs. 64.5%, p = 0.004) and 5.22 kb of D-DR4 (66.1 vs. 41.7%, p = 0.03) among the patients. Segregation analysis showed that the association of the D-DQw4/8/9 and D-DR4 with the diseases was not responsible for the increased frequency of C4 gene deletion in the patients. The decreased concentration of C4 in sera in C4 gene-deleted patients might be directly involved in the pathogenesis of IgAN and HSPN.

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Section: Introductionmentioning

confidence: 99%

Genetic Study on HLA Class II and Class III Region in the Disease Associated with IgA Nephropathy

Abe¹,

Kohsaka

Tanaka³

et al. 1993

Nephron

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“…This study brings some evidence that not only the B18,BfF1 haplotype, as suggested in previous studies [9][10][11][12][13], but also the silent complement factor allele C4BQO by itself characterise a particularly early-onset form of Type 1 diabetes occurring mostly before 6 years of age. Conversely, the B8, DR3 haplotype has been observed to occur more often in patients older than 6 years at onset.…”

Section: Discussionmentioning

confidence: 50%

“…The most widely confirmed association is that of early onset with the properdin factor B allele BfF1 [9][10][11][12]. In a previous study [13], we also have found a strong association with HLA-B18 but not with the B18,BfF1,DR3 haplotype, possibly because of the small sample size.…”

mentioning

confidence: 69%

“…Although DR3 as an entity has been reported to be independent of age at onset [15], indirect evidence has suggested its heterogeneity. On the one hand, BfF1 and B18 are in linkage disequilibrium with DR3 [18,23] -a haplotype more common in patients of Mediterranean than of Northern European origin [11]; on the other hand, the B8,DR3 haplotype has been found increased in diabetic patients with associated autoimmune manifestations who usually develop the disease after 30 years of age [24,25].…”

Section: Discussionmentioning

confidence: 99%

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Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in Type 1 (insulin-dependent) diabetes

et al. 1988

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Summary. Heterogeneity between two haplotypes in linkage disequilibrium with DR3: B8, C4AQOBt,BfS,DR3 and B18,C4A3BQO,BfF1,DR3, with regard to age at onset of Type 1 (insulin-dependent) diabetes mellitus, was investigated in 325 unrelated French patients (146 males and 179 females, age at onset 1 month to 29 years) who were genotyped for HLA-A, B, C, DR and Bf and 225 of whom were typed for the C4A, B complement components. A subgroup of 82 patients and 75 control subjects were tested for DR[3 and DQ[~ DNA restriction fragment length polymorphism. The distribution according to age at onset and the mean ages at onset were compared between patients bearing B8, DR3 (n=58), B18,DR3 (n=62) or other DR3 haplotypes (Bx, DR3, n=70), the haplotype segments C4AQOB1,DR3 (n=41) or C4A3BQO,DR3 (n=52) and the C4 null alleles C4AQO (N=48) or C4BQO (n= 112) alone. The BS,DR3 haplotype, its smaller segment C4AQOB1,DR3 or C4AQO alone were associated with age at onset after 6 years (p<0.01, <0.08 and < 0.02 respectively); on the other hand, the B18,DR3 haplotype, its segment C4A3BQO,DR3 or C4BQO alone were significantly more frequent in patients aged less than 6 years at onset (t9< 0.02, < 0.01 and < 0.01 respectively). Accordingly, the mean age of onset was significantly lower in the latter compared with the former pattens (p< 0.02, < 0.02 and < 0.01 respectively). No age-related variation was observed in BX,DR3 patients and their mean age of onset was intermediate. The observed age distributions were sex dependent: that of C4AQO was mainly observed in males, that of C4BQO in females. Restriction fragment length polymorphism analysis in 37 patients and 32 control subjects positive for DR3 showed distinct patterns which correlated with DR3 and/or DQW2 borne by the B8 (n= 11) and the B18 (n= 18) haplotypes, respectively. BX,DR3 subjects exhibited either one or the other of these patterns. In the patients, the B18 associated fragments were found in most cases; whereas the B8 associated pattern was more frequent in the control subjects. These results provide evidence that a heterogeneous genetic background associated with two subsets of DR3 and/or silent alleles of the fourth component of complement could account for differences in the clinical expression of Type 1 diabetes.

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“…In fact, long genomic extensions termed conserved extended haplotypes (CEH) or ancestral haplotypes that have been maintained unaltered during human evolution are characteristic of this genomic region (4). A particular HLA-DR3 CEH (A*30-B*18-MICA*4-F1C30-DRB1*0301-DQB1*0201-DPB1*0202, or B18-DR3) that is relatively common in southern European populations, has been shown to be conserved across a 5 Mb region and to be more diabetogenic than other HLA-DR3 chromosomes (5,6). These findings support the hypothesis that B18-DR3 chromosomes carry additional risk alleles in other susceptibility loci , which are fixed in all B18-DR3 CEHs, but may not be always present in other less-predisposing DR3 chromosomes.…”

Section: Introductionmentioning

confidence: 99%

Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA

et al. 2009

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Objective To identify additional diabetes susceptibility markers in the MHC that could be responsible for the differential diabetogenicity of different HLA-DR3 CEHs. Research Design and Methods High resolution SNP genotyping of the MHC was performed in 15 T1D patients and 39 non-diabetic controls, homozygous for DR3-DQ2 and with one copy of the A*30-B*18-MICA*4-F1C30-DRB1*0301-DQB1*0201-DPB1*0202 HLA haplotype. Significantly associated SNPs were replicated in an independent sample of 554 T1D patients and 841 controls without HLA matching. Electrophoretic mobility shift assay was used to demonstrate a functional effect of an associated SNP. Results Seven SNPs showed evidence of association in the initial discovery experiment. Upon replication, only rs419434 (upstream HLA-DOA gene) remained significant. A functional variant (rs432375) in complete LD with rs419434 was shown to affect USF-1 binding and could be responsible for the association signal in the region. Conclusions We have identified a novel susceptibility locus within the MHC with a modest contribution to T1D (OR= 1.93; CI: 1.52-2-44; p=10−8) that is independent of HLA-DRB1 locus.

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HLA‐A, B, C, DR antigens, Bf, C4 and glyoxalase I (GLO) polymorphisms in French Basques with insulin‐dependent diabetes mellitus (IDDM)

Cited by 55 publications

References 2 publications

Genetic Study on HLA Class II and Class III Region in the Disease Associated with IgA Nephropathy

Genetic Study on HLA Class II and Class III Region in the Disease Associated with IgA Nephropathy

Two distinct HLA-DR3 haplotypes are associated with age related heterogeneity in Type 1 (insulin-dependent) diabetes

Exploring the diabetogenicity of the HLA-B18-DR3 CEH: independent association with T1D genetic risk close to HLA-DOA

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