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HLA-DPB1 alleles in African-Americans and Afro-Caribbeans: Distribution and haplotype associations
14
Abstracts
B 2.1.15
GENOMIC CHARACTERIZATION OF DOW4 ALLELES ASSOCIATED WITH DR3(~I8) IN AFRICAN AMEEICANS. N Berka, G Dunston, C Hurley, E Koh and A Johnson,
Immunogenetics laboratory, Howard University, and Immunogenetics laboratory, Georgetown University, Washington, D.C. This study describes the diversity of the DRw18 haplotype in the American black population. Previous studies in our laboratory , using serology, cellular typing, and restriction fragment length polymorphism (RFLP) analysis showed that the DRw18 is commonly associated with DQw4 in African Americans. In this report, the polymerase chain reaction and a chemiluminescent detection system were used to characterize the DQw4 alleles. Two oligonucleotide probes (2301, 2302) from the llth IHW, were used to distinguish the DQw4 alleles (DQBI.0401, DQB1.0402). As expected, our results showed that all DQw4 were associated with DRwlS~ More importantly, DQBI.0401 was totally absent in a panel of 35 African American that carry the DRwI8 specificity, whereas DQBI.0402 was associated with 35/35 (100%) DRwI8. Thus, we conclude that the predominant haplotype in African Americans is DRBI.0302, DQBI.0402. From a clinical perspective, the rarity of this haplotype among Caucasians greatly decreases the likelihood of finding a compatible HLA match from this population and underscores the importance of increasin E the number of organ donors from the Afrlcan-Amerlcan population. Moreover, the effect on long-term graft survival of the DQw4 polymorphism remains to be determined. It seems that once the latter haplotype appeared in the population, natural selection operated to maintain the stability of this haplotype.
C 2.1.16
HLA-DPB 1 ALLELES IN AFRICAN-AMERICANS AND AFROCARIBBEANS: DISTRIBUTION AND HAPLOTYPE ASSOCIATIONS. P.A.Fraser, D. Fici, D. Boyd, E.J. Yunis, C.A. Alper and Z. Awdeh, The Center for Blood Research, Harvard Medical School, Boston, MA. In our continued efforts to def'me MHC alleles and extended MHC haplotypes in populations of black African descent, we report a pilot study of DNA typing for HLA-DPB 1 alleles in 50 unrelated African-Americans and Afro-Caribbeans. In this small sample, there were 23 rheumatoid arthritis (RA), 2 systemic lupus erythematosus (SLE) patients and 25 healthy individuals who had previously participated in our family studies. We did not detect any deviation in the distribution of DPB 1 alleles in our RA and SLE patients when compared to previous reports in normal black populations, or when compared to our healthy subjects. Pooled DPB 1 frequencies from RA, SLE and healthy subjects formed the basis for this analysis. DPBI*0101, the most prevalent allele, occurred in 30 (60%) subjects. This frequency may include HLA-DPBI* WA2 and DPBI*WA3, since we did not test specifically for these West African alleles which are related to DPB 1"0101 (Tissue Antigens 1992:39; 144). Frequencies of other common (antigen frequency > 10%) alleles- DPBI*0401, *0402 ,*0201 and "1301 were 26%, 26%, 14% and 10%, respectively. Except for DPBI*1701 (8%), the overall distribution of DPBI and the absence of DPBI*0501, "0801, "0901, *1001, "1501, "1901, DPB7, DPB12, DPB20, DPB21, DPB22 were consistent with previous reports of HLA-DPB 1 in Blacks (HumanImmunol 1991:30;60). Preliminary segregation analyses show that one common haplotype HLA-DRB 1'0302, DQB 1"0402 occurred with all of the most common DPB 1 alleles-DPB 1*0101, DPB 1"0401 and DPB 1"0402. Further studies are needed to determine whether the def'mition of extended MHC haplotypes in populations of black African descent includes the HLA-DPB 1 locus.
Abstracts
B 2.1.15
GENOMIC CHARACTERIZATION OF DOW4 ALLELES ASSOCIATED WITH DR3(~I8) IN AFRICAN AMEEICANS. N Berka, G Dunston, C Hurley, E Koh and A Johnson,
Immunogenetics laboratory, Howard University, and Immunogenetics laboratory, Georgetown University, Washington, D.C. This study describes the diversity of the DRw18 haplotype in the American black population. Previous studies in our laboratory , using serology, cellular typing, and restriction fragment length polymorphism (RFLP) analysis showed that the DRw18 is commonly associated with DQw4 in African Americans. In this report, the polymerase chain reaction and a chemiluminescent detection system were used to characterize the DQw4 alleles. Two oligonucleotide probes (2301, 2302) from the llth IHW, were used to distinguish the DQw4 alleles (DQBI.0401, DQB1.0402). As expected, our results showed that all DQw4 were associated with DRwlS~ More importantly, DQBI.0401 was totally absent in a panel of 35 African American that carry the DRwI8 specificity, whereas DQBI.0402 was associated with 35/35 (100%) DRwI8. Thus, we conclude that the predominant haplotype in African Americans is DRBI.0302, DQBI.0402. From a clinical perspective, the rarity of this haplotype among Caucasians greatly decreases the likelihood of finding a compatible HLA match from this population and underscores the importance of increasin E the number of organ donors from the Afrlcan-Amerlcan population. Moreover, the effect on long-term graft survival of the DQw4 polymorphism remains to be determined. It seems that once the latter haplotype appeared in the population, natural selection operated to maintain the stability of this haplotype.
C 2.1.16
HLA-DPB 1 ALLELES IN AFRICAN-AMERICANS AND AFROCARIBBEANS: DISTRIBUTION AND HAPLOTYPE ASSOCIATIONS. P.A.Fraser, D. Fici, D. Boyd, E.J. Yunis, C.A. Alper and Z. Awdeh, The Center for Blood Research, Harvard Medical School, Boston, MA. In our continued efforts to def'me MHC alleles and extended MHC haplotypes in populations of black African descent, we report a pilot study of DNA typing for HLA-DPB 1 alleles in 50 unrelated African-Americans and Afro-Caribbeans. In this small sample, there were 23 rheumatoid arthritis (RA), 2 systemic lupus erythematosus (SLE) patients and 25 healthy individuals who had previously participated in our family studies. We did not detect any deviation in the distribution of DPB 1 alleles in our RA and SLE patients when compared to previous reports in normal black populations, or when compared to our healthy subjects. Pooled DPB 1 frequencies from RA, SLE and healthy subjects formed the basis for this analysis. DPBI*0101, the most prevalent allele, occurred in 30 (60%) subjects. This frequency may include HLA-DPBI* WA2 and DPBI*WA3, since we did not test specifically for these West African alleles which are related to DPB 1"0101 (Tissue Antigens 1992:39; 144). Frequencies of other common (antigen frequency > 10%) alleles- DPBI*0401, *0402 ,*0201 and "1301 were 26%, 26%, 14% and 10%, respectively. Except for DPBI*1701 (8%), the overall distribution of DPBI and the absence of DPBI*0501, "0801, "0901, *1001, "1501, "1901, DPB7, DPB12, DPB20, DPB21, DPB22 were consistent with previous reports of HLA-DPB 1 in Blacks (HumanImmunol 1991:30;60). Preliminary segregation analyses show that one common haplotype HLA-DRB 1'0302, DQB 1"0402 occurred with all of the most common DPB 1 alleles-DPB 1*0101, DPB 1"0401 and DPB 1"0402. Further studies are needed to determine whether the def'mition of extended MHC haplotypes in populations of black African descent includes the HLA-DPB 1 locus.