The genetic predisposition to insulin dependent diabetes mellitus (IDDM) among Filipinos was examined by PCR/SSOP typing of 90 patients for the HLA DRB1, DQB1, DPA1, DPB1, -A, -B, and C loci as well as 94 general population controls. These patients have been previously characterized for C-peptide and autoantibodies to islet cell autoantigens. This population contains an unusual DR-DQ haplotype (DRB1*0405-DQB1*0503), with a DRB1 allele (*0405) positively associated in other populations with diabetes and DQA1 and DQB1 alleles (*0101-*0503) that are negatively associated. As found in previous studies of IDDM patients, specific DR-DQ haplotypes or alleles could be identified as susceptible, neutral or protective based on the distribution among Filipino patients and controls. The DR3 and DR9 haplotypes both show dramatic increases among patients (0.161 vs. 0.053 and 0.156 vs. 0.043). The common DR2 haplotype (*1502-*0502) is only slightly decreased. There is a hierarchy of IDDM association among the DR4 haplotypes. The high risk haplotypes are the very rare DRB1*0405-DQB*0302 and DQB1 0405-DQB1*0201, followed by the more common DRB1*0405-DQB1*0401 and DRB1*0405-DQB1*0402. The DRB1*0403-DQB1*0302 is protective. The DRB1*0405-DQB1*05031 haplotype unique to Filipinos, appears to be "neutral" indicating that some Asp57 alleles (DQB1*0503) on the DRB1*0405 haplotype may be neutral while others (DQB1*0401/02) may confer susceptibility. As noted in studies of Caucasian patients, the DPB1*0202 allele was significantly increased among Filipino patients (0.10 vs. 0.04). Among HLA class 1 alleles, the HLA-A*2402 and 2403 were increased among patients while 2407 is decreased. The increase of A*2402 (0.333 vs. 0.213) was not attributable to linkage disequilibrium (LD) with high risk DR-DQ haplotypes. A*3303 was slightly increased due to LD with DR3. The combination of A*2402 and DR3 was associated with higher risk than the A*3303-DR3 haplotype. B*5801 is increased in patients (0.128 vs.. 0.069 in controls) while B*1301 is decreased (0.022 vs. 0.053). The HLA-C*0102 was increased among patients (0.089 vs. 0.037) while C*1502 was decreased (0.028 vs. 0.080). Overall, HLA class I alleles, as well as class II alleles, appear to play a role in determining type 1 diabetes risk in this population. © 2001 Blackwell Science Ltd.
Analysis of the HLA class I and class II susceptibility to type 1 diabetes in filipinos using the PCR-SSOP reverse line blot method / Bugawan, T.L., Alejandrino, M., Ching, J., Klitz, W., Panelo, A., Solfelix, C.M., Buzzetti, R., Pozzilli, P., Erlich, H.A.. - In: EUROPEAN JOURNAL OF IMMUNOGENETICS. - ISSN 0960-7420. - 28:2(2001), p. 289.
Analysis of the HLA class I and class II susceptibility to type 1 diabetes in filipinos using the PCR-SSOP reverse line blot method
Buzzetti R.;Pozzilli P.;
2001
Abstract
The genetic predisposition to insulin dependent diabetes mellitus (IDDM) among Filipinos was examined by PCR/SSOP typing of 90 patients for the HLA DRB1, DQB1, DPA1, DPB1, -A, -B, and C loci as well as 94 general population controls. These patients have been previously characterized for C-peptide and autoantibodies to islet cell autoantigens. This population contains an unusual DR-DQ haplotype (DRB1*0405-DQB1*0503), with a DRB1 allele (*0405) positively associated in other populations with diabetes and DQA1 and DQB1 alleles (*0101-*0503) that are negatively associated. As found in previous studies of IDDM patients, specific DR-DQ haplotypes or alleles could be identified as susceptible, neutral or protective based on the distribution among Filipino patients and controls. The DR3 and DR9 haplotypes both show dramatic increases among patients (0.161 vs. 0.053 and 0.156 vs. 0.043). The common DR2 haplotype (*1502-*0502) is only slightly decreased. There is a hierarchy of IDDM association among the DR4 haplotypes. The high risk haplotypes are the very rare DRB1*0405-DQB*0302 and DQB1 0405-DQB1*0201, followed by the more common DRB1*0405-DQB1*0401 and DRB1*0405-DQB1*0402. The DRB1*0403-DQB1*0302 is protective. The DRB1*0405-DQB1*05031 haplotype unique to Filipinos, appears to be "neutral" indicating that some Asp57 alleles (DQB1*0503) on the DRB1*0405 haplotype may be neutral while others (DQB1*0401/02) may confer susceptibility. As noted in studies of Caucasian patients, the DPB1*0202 allele was significantly increased among Filipino patients (0.10 vs. 0.04). Among HLA class 1 alleles, the HLA-A*2402 and 2403 were increased among patients while 2407 is decreased. The increase of A*2402 (0.333 vs. 0.213) was not attributable to linkage disequilibrium (LD) with high risk DR-DQ haplotypes. A*3303 was slightly increased due to LD with DR3. The combination of A*2402 and DR3 was associated with higher risk than the A*3303-DR3 haplotype. B*5801 is increased in patients (0.128 vs.. 0.069 in controls) while B*1301 is decreased (0.022 vs. 0.053). The HLA-C*0102 was increased among patients (0.089 vs. 0.037) while C*1502 was decreased (0.028 vs. 0.080). Overall, HLA class I alleles, as well as class II alleles, appear to play a role in determining type 1 diabetes risk in this population. © 2001 Blackwell Science Ltd.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
