- Email: [email protected]
175-P: Genetic diversity of the HLA-G coding-region in Amerindian populations from the Brazilian Amazon region
S94
Abstracts
175-P
GENETIC DIVERSITY OF THE HLA-G CODING-REGION IN AMERINDIAN POPULATIONS FROM THE BRAZILIAN AMAZON REGION. Celso T. Mendes-Junior,1 Erick C. Castelli,1 Ca´ssia M. Paula-Santos,1 Aguinaldo L. Simo˜es,2 Eduardo A. Donadi.1 1Department of Medicine, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeirao Preto, SP, Brazil; 2Department of Genetics, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeirao Preto, SP, Brazil. Aim: HLA-G plays an important role in the modulation of the maternal immune system during pregnancy and evidence of balancing selection acting at the promoter and 3’UTR regions has already been reported. Aiming at verifying the existence of selection acting in the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were evaluated in 142 Amerindians from 5 isolated tribes that inhabit the Central Amazon. Methods: Six previously described SNPs were identified and the EM and PHASE algorithms were used to reconstruct SNP haplotypes (HLA-G alleles). Results: A new HLA-G allele, originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. A second crossing-over event that originated the association between the *010102 allele and 14-bp deletion was also detected. These findings corroborate the turnover model that postulates that the joint action of genetic drift and balancing natural selection result in the maintenance of new alleles, often generated by gene conversion in response to a newly colonized environment. In fact, the Ewens-Watterson’s test of neutrality was performed and the results suggest balancing selection (heterozygote advantage) operating on HLA-G alleles. Conclusions: Such results corroborate the trend toward balancing selection previously uncovered by the analysis of the HLA-G 14-bp insertion/deletion polymorphism in these same populations, emphasizing the functional relevance of HLA-G antigens for reproductive success in isolated indigenous populations.
177-P
ASSOCIATION OF HLA-DR-DQ HAPLOTYPES WITH JUVENILE IDIOPATHIC ARTHRITIS (JIA). Jill Hollenbach,1 Teodorica Bugawan,2 Marc Sudman,3 Glenys Thomson,4 Susan Thompson,3 Mimi Ryan,3 Carl Langefeld,5 Henry Erlich,2 David Glass.3 1Center for Genetics, Children’s Hospital Oakland Research Institute, Oakland, CA, USA; 2Human Genetics, Roche Molecular Systems, Pleasanton, CA, USA; 3 William S. Rowe Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 4UC Berkeley, Berkeley, CA, USA; 5Dept of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA. Aim: We estimated and tested for the association of HLA-DR-DQ polymorphism with JIA under a casecontrol design. Methods: HLA class I and class II loci were genotyped using a immobilized probe (linear array) method in 820 cases (poly-articular and oligo-articular) and 273 controls. DRB1-DQB1 haplotype frequencies were estimated by EM methods and the frequencies in cases and controls were compared. Results: Three DR-DQ haplotypes were significantly associated with JIA (DRB1*0801-DQB1*0402, OR ⫽ 5.86, 3.16-10.87; DRB1*1103/4-DQB1*0301, OR ⫽ 4.93, 2.65-9.18; and DRB1*1301-DQB1*0603, OR ⫽ 1.81, 1.22-2.69). DRB1*1101-DQB1*0301 was not associated, suggesting a critical role for DRB1. The most common protective haplotype was DRB1*1501-DQB1*0602 (OR ⫽ 0.40, 0.29-0.55). Conclusions: Several DR-DQ haplotypes are associated with an increased risk and one common haplotype decreased risk to JIA.
Abstracts
175-P
GENETIC DIVERSITY OF THE HLA-G CODING-REGION IN AMERINDIAN POPULATIONS FROM THE BRAZILIAN AMAZON REGION. Celso T. Mendes-Junior,1 Erick C. Castelli,1 Ca´ssia M. Paula-Santos,1 Aguinaldo L. Simo˜es,2 Eduardo A. Donadi.1 1Department of Medicine, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeirao Preto, SP, Brazil; 2Department of Genetics, School of Medicine of Ribeira˜o Preto, University of Sa˜o Paulo, Ribeirao Preto, SP, Brazil. Aim: HLA-G plays an important role in the modulation of the maternal immune system during pregnancy and evidence of balancing selection acting at the promoter and 3’UTR regions has already been reported. Aiming at verifying the existence of selection acting in the HLA-G coding region in the Amazon Rainforest, exons 2, 3 and 4 were evaluated in 142 Amerindians from 5 isolated tribes that inhabit the Central Amazon. Methods: Six previously described SNPs were identified and the EM and PHASE algorithms were used to reconstruct SNP haplotypes (HLA-G alleles). Results: A new HLA-G allele, originated in Amerindian populations by a crossing-over event between two widespread HLA-G alleles, was identified in 18 individuals. A second crossing-over event that originated the association between the *010102 allele and 14-bp deletion was also detected. These findings corroborate the turnover model that postulates that the joint action of genetic drift and balancing natural selection result in the maintenance of new alleles, often generated by gene conversion in response to a newly colonized environment. In fact, the Ewens-Watterson’s test of neutrality was performed and the results suggest balancing selection (heterozygote advantage) operating on HLA-G alleles. Conclusions: Such results corroborate the trend toward balancing selection previously uncovered by the analysis of the HLA-G 14-bp insertion/deletion polymorphism in these same populations, emphasizing the functional relevance of HLA-G antigens for reproductive success in isolated indigenous populations.
177-P
ASSOCIATION OF HLA-DR-DQ HAPLOTYPES WITH JUVENILE IDIOPATHIC ARTHRITIS (JIA). Jill Hollenbach,1 Teodorica Bugawan,2 Marc Sudman,3 Glenys Thomson,4 Susan Thompson,3 Mimi Ryan,3 Carl Langefeld,5 Henry Erlich,2 David Glass.3 1Center for Genetics, Children’s Hospital Oakland Research Institute, Oakland, CA, USA; 2Human Genetics, Roche Molecular Systems, Pleasanton, CA, USA; 3 William S. Rowe Division of Rheumatology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA; 4UC Berkeley, Berkeley, CA, USA; 5Dept of Biostatistical Sciences, Wake Forest University Health Sciences, Winston-Salem, NC, USA. Aim: We estimated and tested for the association of HLA-DR-DQ polymorphism with JIA under a casecontrol design. Methods: HLA class I and class II loci were genotyped using a immobilized probe (linear array) method in 820 cases (poly-articular and oligo-articular) and 273 controls. DRB1-DQB1 haplotype frequencies were estimated by EM methods and the frequencies in cases and controls were compared. Results: Three DR-DQ haplotypes were significantly associated with JIA (DRB1*0801-DQB1*0402, OR ⫽ 5.86, 3.16-10.87; DRB1*1103/4-DQB1*0301, OR ⫽ 4.93, 2.65-9.18; and DRB1*1301-DQB1*0603, OR ⫽ 1.81, 1.22-2.69). DRB1*1101-DQB1*0301 was not associated, suggesting a critical role for DRB1. The most common protective haplotype was DRB1*1501-DQB1*0602 (OR ⫽ 0.40, 0.29-0.55). Conclusions: Several DR-DQ haplotypes are associated with an increased risk and one common haplotype decreased risk to JIA.