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H Debaz

Publications and source records attributed to H Debaz.

5 recordsLinked to original sources
PubMed2000

Contribution of HLA class II genes to end stage renal disease in mexican patients with type 2 diabetes mellitus.

To analyze the contribution of MHC class II genes in type 2 diabetes mellitus (DM) with end stage renal disease (ESRD), we examined the distribution of HLA-DRB1, DQA1, DQB1 loci in Mexican Mestizos of Central Mexico, using PCR-SSOP and PCR-SSP. Three groups were included: 47 type 2 diabetic ESRD patients; 42 patients with ESRD and 50 type 2 DM patients with no kidney complication. The results were compared with those of 101 controls of the same area. The median since DM was first diagnosed, was 18 years prior to the onset of ESRD. The frequencies of DRB1*1502 and DQB1*0501 were increased in DM patients with ESRD (p = 0.004; RR = 7.4, CI = 1.5-37; EF = 0. 13; p = 0.007; RR = 2.9, CI = 2.3-3.5, EF = 0.21, respectively). In contrast, DRB1*0407 was decreased in the same group (p = 0.0008, RR = 0.2; CI = 0.035-0.70, PF = 0.19). Diabetic patients with DRB1*1502 are 8.8 times more likely to develop ESRD, independently of the duration time of DM. DRB1*1502 contributes to the susceptibility to ESRD while DRB1*0407 is involved in protection. The residue at DRB1-74 differs in these alleles: DRB1*0407 has glutamic acid and DRB1*1502 has an alanine, suggesting that this substitution may be important for both, peptide anchoring and for presentation to the T cells.

Adult↗
PubMed1998

MHC class II sequences of susceptibility and protection in Mexicans with autoimmune hepatitis.

BACKGROUND/AIMS: Autoimmune hepatitis has a genetic background associated with different HLA DRB1 alleles depending on the ethnic group. The aim of this study was to analyse the immunogenetics of type I autoimmune hepatitis in Mexicans. METHODS: Thirty Mexican Mestizo patients and 175 healthy controls were HLA typed as follows: class I antigens were determined by microlymphocytotoxicity and class II typing was done on DNA samples using PCR-SSO and PCR-SSP for DRB1, DQA1 and DQB1 loci. RESULTS: A significant association of autoimmune hepatitis with DRB1*0404 was found, (chi2Y=19.95, pc=0.002, RR=7.71), suggesting the presence of a susceptibility gene located at the DRB1 locus. Resistance was at least partially due to a DQB1 gene, since a significant decrease in DQB1*0301 was also detected (chi2Y=8.21, pc=0.04). Analysis of subgroups according to age at onset showed an association with DRB1*0404 (chi2Y=4.31, p=0.04) in patients with late onset (after 30 years), while DQA1*0501 (chi2Y=5.12, p=0.02) was increased in the early onset group. CONCLUSIONS: The possible mechanism of HLA association is due to "shared epitopes", since DRB1*0404, and those found in other populations namely, DRB1*0401, *0405 and *0301 share almost the same sequence at position 67-72 (LLEQRR, R or K at 71). Valine-86 is also relevant to the age at onset because DRB1*0404 is increased in the patients with an average age at onset of 32. These findings are relevant in determining which peptides in the liver are targets for T cells.

Adult↗
PubMed1998

Relevant residues of DRbeta1 third hypervariable region contributing to the expression and to severity of rheumatoid arthritis (RA) in Mexicans.

Rheumatoid arthritis (RA) is a chronic autoimmune disease leading to destruction of the joints. Residues at positions 67-74 of the DRB1 third hypervariable region are involved in susceptibility (S) and resistance (P) to RA. DNA from 83 patients and 175 controls, all of them Mexican Mestizos were oligotyped using PCR-SSOP and PCR-SSP. The (S) alleles are DRB*0404 (p = 0.000004), *0401 (p = 0.007) and *1001 (p = 0.008). Those associated with P are DRB1*0701 (p = 0.0001); *1101 (p = 0.01); *1503 (p = 0.02); *0801 (p = 0.04); *1401 (p = 0.04). Susceptibility/protection are recessive traits; SS genotypes are increased in the patients (p = 0.0003) while PP genotypes are decreased in them (p = 0.00004). The motif at 67-74 and the valine or glycine at position 86 are relevant in the development and severity of RA in Mexicans. The associations suggest that residues 67, 70, 71 are central for susceptibility. The P alleles have D-70 or carry V-86 in the absence of D-70. Thus, susceptibility/protection depends on the combination of basic residues at these positions and a non-polar aa at 86 contributes to resistance. Severity is also HLA influenced. DQA1*03011-DQB1*0302 are associated to severe lesions in the presence of any DR4 subtype. Analyzing different ethnic groups is essential to elucidate the etiopathogenesis of RA.

Adult↗
PubMed1997

[High- and low-risk molecular sequences in autoimmune diseases. An analysis of type I diabetes in Latin America].

Type I diabetes is an autoimmune and a polygenic disease, in which MHC-class II genes contribute to 48% of the disease. The aim of the present study, is to provide a guideline to understanding the molecular association of these genes, through the immunogenetic analysis of 3 Latin american mestizo populations. We included 606 individuals, 349 patients with DMDI and 257 healthy controls coming from 3 geographical areas: Mexico City, Mexico; Caracas, Venezuela and Medellin, Colombia. The results clearly indicate that in mestizo groups, the diabetogenic haplotypes are from mediterranean ancestry, while protection is due to Amerindian genes. It was demonstrated that the relevant sequences for IDDM expression are located to DRB1 and DQB1 loci with a minimal contribution of DQA1 residues. The sequences determining peptide recognition and the induction of TH1 cells mediating the cellular autoimmune response are in positions DRB1-57 and 74 (an aspartic acid and a glutamic acid respectively, confer protection), modulated by D-57 in the DQ, 8 chain. These data show that DRB1-DQB1 haplotypes are central for IDDM expression and open new pathways for the disease management.

Adolescent↗