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HLA-DQ and DPB1 alleles on HLA-DQW2 and HLA-DQW9 extended haplotypes
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Abstracts
B 5.2.59
UNIQUE DRBI*0302,DQBI*0402 HAPLOTYPE IN AFRICAN-AMERICANS IS ASSOCIATED WITH RESISTANCE TO INSULIN DEPENDENT DIABETES MELLITUS. GM Dunston~ G Bland, P Furbert-Harris, D Parish-Gause, N Berka and A Glasgow, Immunogenetics Laboratory, Howard University, Washington, DC. This study further characterizes, by oligonucleotide typing, a previously reported DR3,DQ polymorphism in African-Americans associated with susceptibility and resistance to insulin dependent diabetes mellitus (IDDM). Twenty-nine African-American IDDM patients, all diagnosed at less than 18 yrs old, were recruited from Howard University and affiliate hospitals in Washington, DC. Racially matched controls were randomly selected from the same geographic area. Genomic DNA from PBLs was tested in dot blot assays using a nonradioactive enzygraphic web technique. PCR primers and probes were from the llth International Histocompatibility Workshop. In controls, the 2 DR3 alleles (0301, 0302) were both common, occurring in almost equal frequencies, 45% and 55%, respectively. Unlike controls, almost all (82%) DR3 patients had the 0301 allele; only 2 (18%) had 0302. Like Caucasians, DRBI,0301 in African-Americans is in linkage disequilibrium with DQBI,0201, while DRBI,0302, which is unique in African-Americans, is almost always linked to DQBI,0402. Of the 2 patients with the 0302 allele, i was associated with DQBI,0402 and the other with DQBI,0201. The latter may be a rare recombinant between DRBI and DQBI. Its noteworthy that DQB* 0402 encodes an aspartic acid in position 57 (Asp57) of the DQ~ chain. The significant decrease of DRBI,0302,DQBI,0402 among IDDM patients (X=5.75, P<0.02) is consistent with observations in Caucasians showing an association of IDDM resistance with DQBI (Asp57). This study shows the value of transracial haplotypes in disease association studies where "unique" polymorphisms in one population can assist in mapping genes underlying susceptibility and/or resistance to disease.
B 5.2.60
HLA-DQ AND DPBI ALLELES ON HLA-DQW2 AND HLA-DQW9 EXTENDED HAPLOTYPES. JJ Yunis, M Salazar, MB Delgado, CA Alper, DH Bing and EJ Yunis. Division of Immunogenetics, Dana-Farber Cancer Institute. The Center for Blood Research, Boston, MA 02115. DQA1, DQB1 and DPB1 alleles were investigated in a large panel of samples carrying HLA-DQw2 and HLA-DQw9-bearing extended haplotypes. Every instance of the [HLA-B8,SC01,DR3,DQw2a]and [HLA-B18,FLC30,DR3,DQw2b]extended haplotypes carried the DQA1"0501 allele, while every instance of the [HLA-B44,FC31, DR7,DQw2c],[HLA-Bw47,FC91,0,DR7,DQw2c]and [HLA-Bw57,SC61,DR7,DQw2d] carried the DQAI*0201allele. All HLA-DR3, DQw2 and HLA-DR7, DQw2 extended haplotypes carried the DQB1 "0201 allele. Every example of the [HLA-Bw57,SC61, DR7, DQw9]carried the DQB1 *0303 allele. Several associations between the DPB1 alleles and some HLA-DQw2 and DQw9-carrying extended haplotypes were identified. HLA-DPw2 encoding alleles, DPB1*0202 (5/10, 50%, p < 0.001) and 0201 (3/10, 30%), were found on the [HLA-B18,FLC30,DR3,DQw2b]extended haplotype. Every instance of the [HLA-Bw57,SC61,DR7,DQw9]extended haplotype carried the DPB1 "0401 allele (6/6, 100%, p >0.05). Also, we have confirmed the association between the DPB1 "0101 and DPB1"0401 alleles with the [HLA-B8,SC01,DR3,DQw'2a]extended haplotype. The analysis of homozygous typing cells carrying the [HLA-B44,FC31,DR7, DQw2c] extended haplotype showed that the DPB1*0401 and 0201 alleles were present at similar frequencies (37.5%), while the DPBI*1101 allele was found in only 25% (2/8, p 0.005) of these haplotypes analyzed. Our results suggest that the constancy between HLA-B, DR, DQ regions sometimes extends to the DP region and that the extent of such fixity could be different, perhaps as the result of ethnic variability of the population studied.
Abstracts
B 5.2.59
UNIQUE DRBI*0302,DQBI*0402 HAPLOTYPE IN AFRICAN-AMERICANS IS ASSOCIATED WITH RESISTANCE TO INSULIN DEPENDENT DIABETES MELLITUS. GM Dunston~ G Bland, P Furbert-Harris, D Parish-Gause, N Berka and A Glasgow, Immunogenetics Laboratory, Howard University, Washington, DC. This study further characterizes, by oligonucleotide typing, a previously reported DR3,DQ polymorphism in African-Americans associated with susceptibility and resistance to insulin dependent diabetes mellitus (IDDM). Twenty-nine African-American IDDM patients, all diagnosed at less than 18 yrs old, were recruited from Howard University and affiliate hospitals in Washington, DC. Racially matched controls were randomly selected from the same geographic area. Genomic DNA from PBLs was tested in dot blot assays using a nonradioactive enzygraphic web technique. PCR primers and probes were from the llth International Histocompatibility Workshop. In controls, the 2 DR3 alleles (0301, 0302) were both common, occurring in almost equal frequencies, 45% and 55%, respectively. Unlike controls, almost all (82%) DR3 patients had the 0301 allele; only 2 (18%) had 0302. Like Caucasians, DRBI,0301 in African-Americans is in linkage disequilibrium with DQBI,0201, while DRBI,0302, which is unique in African-Americans, is almost always linked to DQBI,0402. Of the 2 patients with the 0302 allele, i was associated with DQBI,0402 and the other with DQBI,0201. The latter may be a rare recombinant between DRBI and DQBI. Its noteworthy that DQB* 0402 encodes an aspartic acid in position 57 (Asp57) of the DQ~ chain. The significant decrease of DRBI,0302,DQBI,0402 among IDDM patients (X=5.75, P<0.02) is consistent with observations in Caucasians showing an association of IDDM resistance with DQBI (Asp57). This study shows the value of transracial haplotypes in disease association studies where "unique" polymorphisms in one population can assist in mapping genes underlying susceptibility and/or resistance to disease.
B 5.2.60
HLA-DQ AND DPBI ALLELES ON HLA-DQW2 AND HLA-DQW9 EXTENDED HAPLOTYPES. JJ Yunis, M Salazar, MB Delgado, CA Alper, DH Bing and EJ Yunis. Division of Immunogenetics, Dana-Farber Cancer Institute. The Center for Blood Research, Boston, MA 02115. DQA1, DQB1 and DPB1 alleles were investigated in a large panel of samples carrying HLA-DQw2 and HLA-DQw9-bearing extended haplotypes. Every instance of the [HLA-B8,SC01,DR3,DQw2a]and [HLA-B18,FLC30,DR3,DQw2b]extended haplotypes carried the DQA1"0501 allele, while every instance of the [HLA-B44,FC31, DR7,DQw2c],[HLA-Bw47,FC91,0,DR7,DQw2c]and [HLA-Bw57,SC61,DR7,DQw2d] carried the DQAI*0201allele. All HLA-DR3, DQw2 and HLA-DR7, DQw2 extended haplotypes carried the DQB1 "0201 allele. Every example of the [HLA-Bw57,SC61, DR7, DQw9]carried the DQB1 *0303 allele. Several associations between the DPB1 alleles and some HLA-DQw2 and DQw9-carrying extended haplotypes were identified. HLA-DPw2 encoding alleles, DPB1*0202 (5/10, 50%, p < 0.001) and 0201 (3/10, 30%), were found on the [HLA-B18,FLC30,DR3,DQw2b]extended haplotype. Every instance of the [HLA-Bw57,SC61,DR7,DQw9]extended haplotype carried the DPB1 "0401 allele (6/6, 100%, p >0.05). Also, we have confirmed the association between the DPB1 "0101 and DPB1"0401 alleles with the [HLA-B8,SC01,DR3,DQw'2a]extended haplotype. The analysis of homozygous typing cells carrying the [HLA-B44,FC31,DR7, DQw2c] extended haplotype showed that the DPB1*0401 and 0201 alleles were present at similar frequencies (37.5%), while the DPBI*1101 allele was found in only 25% (2/8, p 0.005) of these haplotypes analyzed. Our results suggest that the constancy between HLA-B, DR, DQ regions sometimes extends to the DP region and that the extent of such fixity could be different, perhaps as the result of ethnic variability of the population studied.