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.
Pérez-Luque
E
E
Department of Immunogenetics, InDRE, SSA, Mexico City, Mexico.
Malacara
J M
JM
Olivo-Díaz
A
A
Aláez
C
C
Debaz
H
H
Vázquez-Garcia
M
M
Garay
M E
ME
Nava
L E
LE
Burguete
A
A
Gorodezky
C
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005260:Female; D005802:Genes, MHC Class II; D020022:Genetic Predisposition to Disease; D006801:Humans; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008800:Mexico / Q000453:epidemiology; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods