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Relationship between the endothelin-1 locus and HLA-A
S40
Abstracts
1.1 #9
SEROLOGICAL ASSIGNMENT OF REPORTED NOVEL HLA–A AND –B ALLELES Martin Gutierrez,1 Hugo A. Araujo,1 Jennifer L. Stoddard,1 Jennifer Ng,1 Robert Hartzman,1 Carolyn Katovich Hurley,1 Marcelo A Fernandez–Vina.1 1C.W. Bill Young/DoD Marrow Donor Program, Georgetown University and Naval Medical Research Center, Kensington, MD The full characterization of all HLA alleles is crucial for designing donor–search strategies in registries containing serological data. Our laboratory has submitted more than 209 new HLA class I and II sequences to the curated IMGT/HLA database. Of these submissions, 166 of them were HLA class I alleles; however, their serological types were not characterized at that time. In this study, we are reporting HLA class I serological assignments of 30 of the aforementioned alleles. The serotypes of these alleles were determined with local and 13th IHW reagents. In summary, these data will faciliate donor searches by providing serological assignment to these novel alleles. TABLE 1 Serological equivalents Cell ID GN00348 GN00279 GN00300 GN00297 GN00346 GN00341 GN00263 GN00272 GN00351 GN00323 GN00110 GN00104 GN00108 GN00103 GN00105 GN00341
1.1 #10
DNA A*01012 A*0235 A*0235 A*0236 A*0238 A*0306 A*2304 A*2422 A*3009 B*0719 B*1531 B*1530 B*1530 B*1533 B*1534 B*1805
Serology A1 A2 A*02011 Not Informative A*0201 Not Informative A2 A3 short A23 short A24 short A30 short B7 short B75 B62 B62 B62 B62 B18 variant
Cell GN00246 GN00242 GN00155 GN00110 GN00160 GN00316 GN00373 GN00370 GN00333 GN00173 GN00088 GN00097 GN00109 GN00107 GN00106 GN00177
DNA B*2716 B*3530 B*38022 B*3910 B*4010 B*4027 B*4030 B*4105 B*4421 B*5002 B*5106 B*5106 B*5108 B*5801 B*1535 B*1539
Serology B27 short extras with B40 B35 B38 B39 B60 B61 B40 B41 short, Bw6 Negative B44 short B45 B51 B5 B51 B58 B15 B*1501 Not Informative
RELATIONSHIP BETWEEN THE ENDOTHELIN–1 LOCUS AND HLA–A M.Tevfik Dorak,1 Gbolahan O. Folayan,1 Elena S. Lobashevsky,1 James Tang,1 Richard A. Kaslow.1 1Dept of Epidemiology & International Health, UAB School of Public Health, Birmingham, Alabama Endothelin–1 is an endothelial growth factor involved in the pathogenesis of hypertension, cardiovascular diseases, chronic nephropathies as well as angiogenesis in malignancies. The gene encoding endothelin–1, EDN1, is on chromosome 6p24.1 between D6S89 and F13A1. EDN1 is approximately 34 –36 cM telomeric to and shows genetic linkage with the HLA complex. It has several single nucleotide polymorphisms in the promoter region, introns and exons. The relationships among these polymorphisms have been worked out extensively. The most polymorphic marker for EDN1, however, is a dinucleotide repeat polymorphism with 11 alleles in Caucasians. Its relationship with other polymorphisms and relationships of any EDN1 polymorphism with HLA alleles have not been studied. If linkage disequilibrium (LD) exists between EDN1 polymorphisms and HLA, this might be the reason for the weak HLA associations with myocardial infarction and hypertension. Furthermore, such LD could also explain part of HLA effect on tumor aggressiveness. We evaluated the EDN1 VNTR polymorphism in 60 IHW reference cell lines and a sample of Caucasian population (n ⫽ 144). The allele frequency distribution in the population sample was very similar to that of a previously reported in a CEPH reference family panel. Allele 9 (201bp) was the most frequent one, followed by allele 8. Out of 51 HLA–A homozygous cell lines, 19 were homozygous at EDN1 (9 for allele 9). The only consistent association was between HLA–A*02 (all alleles pooled) and EDN1 allele 9. Six cell lines homozygote for HLA–A*02 were also homozygous for EDN1 allele 9 however 16 others had different EDN1 genotypes despite being A*02 homozygote. No significant LD was observed between EDN1 and HLA–A alleles. Although lacking enough statistical power to completely rule out LD, these findings did not suggest strong LD between EDN1 and HLA–A. Therefore, HLA class I associations in cardiovascular diseases and cancer may not be attributed to EDN1.
Abstracts
1.1 #9
SEROLOGICAL ASSIGNMENT OF REPORTED NOVEL HLA–A AND –B ALLELES Martin Gutierrez,1 Hugo A. Araujo,1 Jennifer L. Stoddard,1 Jennifer Ng,1 Robert Hartzman,1 Carolyn Katovich Hurley,1 Marcelo A Fernandez–Vina.1 1C.W. Bill Young/DoD Marrow Donor Program, Georgetown University and Naval Medical Research Center, Kensington, MD The full characterization of all HLA alleles is crucial for designing donor–search strategies in registries containing serological data. Our laboratory has submitted more than 209 new HLA class I and II sequences to the curated IMGT/HLA database. Of these submissions, 166 of them were HLA class I alleles; however, their serological types were not characterized at that time. In this study, we are reporting HLA class I serological assignments of 30 of the aforementioned alleles. The serotypes of these alleles were determined with local and 13th IHW reagents. In summary, these data will faciliate donor searches by providing serological assignment to these novel alleles. TABLE 1 Serological equivalents Cell ID GN00348 GN00279 GN00300 GN00297 GN00346 GN00341 GN00263 GN00272 GN00351 GN00323 GN00110 GN00104 GN00108 GN00103 GN00105 GN00341
1.1 #10
DNA A*01012 A*0235 A*0235 A*0236 A*0238 A*0306 A*2304 A*2422 A*3009 B*0719 B*1531 B*1530 B*1530 B*1533 B*1534 B*1805
Serology A1 A2 A*02011 Not Informative A*0201 Not Informative A2 A3 short A23 short A24 short A30 short B7 short B75 B62 B62 B62 B62 B18 variant
Cell GN00246 GN00242 GN00155 GN00110 GN00160 GN00316 GN00373 GN00370 GN00333 GN00173 GN00088 GN00097 GN00109 GN00107 GN00106 GN00177
DNA B*2716 B*3530 B*38022 B*3910 B*4010 B*4027 B*4030 B*4105 B*4421 B*5002 B*5106 B*5106 B*5108 B*5801 B*1535 B*1539
Serology B27 short extras with B40 B35 B38 B39 B60 B61 B40 B41 short, Bw6 Negative B44 short B45 B51 B5 B51 B58 B15 B*1501 Not Informative
RELATIONSHIP BETWEEN THE ENDOTHELIN–1 LOCUS AND HLA–A M.Tevfik Dorak,1 Gbolahan O. Folayan,1 Elena S. Lobashevsky,1 James Tang,1 Richard A. Kaslow.1 1Dept of Epidemiology & International Health, UAB School of Public Health, Birmingham, Alabama Endothelin–1 is an endothelial growth factor involved in the pathogenesis of hypertension, cardiovascular diseases, chronic nephropathies as well as angiogenesis in malignancies. The gene encoding endothelin–1, EDN1, is on chromosome 6p24.1 between D6S89 and F13A1. EDN1 is approximately 34 –36 cM telomeric to and shows genetic linkage with the HLA complex. It has several single nucleotide polymorphisms in the promoter region, introns and exons. The relationships among these polymorphisms have been worked out extensively. The most polymorphic marker for EDN1, however, is a dinucleotide repeat polymorphism with 11 alleles in Caucasians. Its relationship with other polymorphisms and relationships of any EDN1 polymorphism with HLA alleles have not been studied. If linkage disequilibrium (LD) exists between EDN1 polymorphisms and HLA, this might be the reason for the weak HLA associations with myocardial infarction and hypertension. Furthermore, such LD could also explain part of HLA effect on tumor aggressiveness. We evaluated the EDN1 VNTR polymorphism in 60 IHW reference cell lines and a sample of Caucasian population (n ⫽ 144). The allele frequency distribution in the population sample was very similar to that of a previously reported in a CEPH reference family panel. Allele 9 (201bp) was the most frequent one, followed by allele 8. Out of 51 HLA–A homozygous cell lines, 19 were homozygous at EDN1 (9 for allele 9). The only consistent association was between HLA–A*02 (all alleles pooled) and EDN1 allele 9. Six cell lines homozygote for HLA–A*02 were also homozygous for EDN1 allele 9 however 16 others had different EDN1 genotypes despite being A*02 homozygote. No significant LD was observed between EDN1 and HLA–A alleles. Although lacking enough statistical power to completely rule out LD, these findings did not suggest strong LD between EDN1 and HLA–A. Therefore, HLA class I associations in cardiovascular diseases and cancer may not be attributed to EDN1.