Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia

F. Sizzano, M. Testi, L. Zito, R. Crocchiolo, M. Troiano, B. Mazzi, G. Turchiano, M. Torchio, C. Pultrone, S. Gregori, R. Chiesa, J. Gaziev, P. Sodani, S. Marktel, A. Amoroso, M. G. Roncarolo, G. Lucarelli, F. Ciceri, M. Andreani, K. Fleischhauer

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Polymorphisms in the 3′ untranslated region (3′UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3′UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3′UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3′UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3′UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3′UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.

Original languageEnglish
Pages (from-to)326-332
Number of pages7
JournalTissue Antigens
Volume79
Issue number5
DOIs
Publication statusPublished - May 2012

Fingerprint

HLA-G Antigens
beta-Thalassemia
Hematopoietic Stem Cell Transplantation
3' Untranslated Regions
Stem cells
Haplotypes
Genes
Genotype
Polymorphism
Base Pairing
Single Nucleotide Polymorphism
Hazards
Nucleotides
Confidence Intervals
Untranslated Regions
Linkage Disequilibrium
Graft vs Host Disease
Blood Donors
Autoimmunity
Mountings

Keywords

  • 3′ untranslated region
  • Genotypes
  • Haplotypes
  • Hematopoietic stem cell transplantation
  • Human leukocyte antigen-G
  • Polymorphisms
  • Population studies
  • Thalassemia

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Genetics

Cite this

Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia. / Sizzano, F.; Testi, M.; Zito, L.; Crocchiolo, R.; Troiano, M.; Mazzi, B.; Turchiano, G.; Torchio, M.; Pultrone, C.; Gregori, S.; Chiesa, R.; Gaziev, J.; Sodani, P.; Marktel, S.; Amoroso, A.; Roncarolo, M. G.; Lucarelli, G.; Ciceri, F.; Andreani, M.; Fleischhauer, K.

In: Tissue Antigens, Vol. 79, No. 5, 05.2012, p. 326-332.

Research output: Contribution to journalArticle

Sizzano, F, Testi, M, Zito, L, Crocchiolo, R, Troiano, M, Mazzi, B, Turchiano, G, Torchio, M, Pultrone, C, Gregori, S, Chiesa, R, Gaziev, J, Sodani, P, Marktel, S, Amoroso, A, Roncarolo, MG, Lucarelli, G, Ciceri, F, Andreani, M & Fleischhauer, K 2012, 'Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia', Tissue Antigens, vol. 79, no. 5, pp. 326-332. https://doi.org/10.1111/j.1399-0039.2012.01862.x
Sizzano, F. ; Testi, M. ; Zito, L. ; Crocchiolo, R. ; Troiano, M. ; Mazzi, B. ; Turchiano, G. ; Torchio, M. ; Pultrone, C. ; Gregori, S. ; Chiesa, R. ; Gaziev, J. ; Sodani, P. ; Marktel, S. ; Amoroso, A. ; Roncarolo, M. G. ; Lucarelli, G. ; Ciceri, F. ; Andreani, M. ; Fleischhauer, K. / Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia. In: Tissue Antigens. 2012 ; Vol. 79, No. 5. pp. 326-332.
@article{a7db093c91ef449192d26295c569ca4b,
title = "Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia",
abstract = "Polymorphisms in the 3′ untranslated region (3′UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3′UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3′UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3′UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3′UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95{\%} confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95{\%} CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3′UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.",
keywords = "3′ untranslated region, Genotypes, Haplotypes, Hematopoietic stem cell transplantation, Human leukocyte antigen-G, Polymorphisms, Population studies, Thalassemia",
author = "F. Sizzano and M. Testi and L. Zito and R. Crocchiolo and M. Troiano and B. Mazzi and G. Turchiano and M. Torchio and C. Pultrone and S. Gregori and R. Chiesa and J. Gaziev and P. Sodani and S. Marktel and A. Amoroso and Roncarolo, {M. G.} and G. Lucarelli and F. Ciceri and M. Andreani and K. Fleischhauer",
year = "2012",
month = "5",
doi = "10.1111/j.1399-0039.2012.01862.x",
language = "English",
volume = "79",
pages = "326--332",
journal = "Tissue Antigens",
issn = "0001-2815",
publisher = "Wiley-Blackwell",
number = "5",

}

TY - JOUR

T1 - Genotypes and haplotypes in the 3′ untranslated region of the HLA-G gene and their association with clinical outcome of hematopoietic stem cell transplantation for beta-thalassemia

AU - Sizzano, F.

AU - Testi, M.

AU - Zito, L.

AU - Crocchiolo, R.

AU - Troiano, M.

AU - Mazzi, B.

AU - Turchiano, G.

AU - Torchio, M.

AU - Pultrone, C.

AU - Gregori, S.

AU - Chiesa, R.

AU - Gaziev, J.

AU - Sodani, P.

AU - Marktel, S.

AU - Amoroso, A.

AU - Roncarolo, M. G.

AU - Lucarelli, G.

AU - Ciceri, F.

AU - Andreani, M.

AU - Fleischhauer, K.

PY - 2012/5

Y1 - 2012/5

N2 - Polymorphisms in the 3′ untranslated region (3′UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3′UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3′UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3′UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3′UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3′UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.

AB - Polymorphisms in the 3′ untranslated region (3′UTR) of HLA-G, an important player in immunological tolerance, could be involved in post-transcriptional expression control, and their association with different clinical immune-related conditions including autoimmunity and transplantation is of mounting interest. Most studies have focused on a 14 base pair (bp) insertion/deletion (ins/del), while additional single-nucleotide polymorphisms (SNPs) in the HLA-G 3′UTR have been described but not extensively investigated for their clinical relevance. Here we have comparatively studied the association between 3′UTR haplotypes of HLA-G, or the 14 bp ins/del, with clinical outcome of HLA-identical sibling hematopoietic stem cell transplantation (HSCT) in 147 Middle Eastern beta-thalassemia patients. Sequence based typing of 3′UTR HLA-G polymorphisms in the patients and in 102 healthy Italian blood donors showed strong linkage disequilibrium between the 14 bp ins/del and five 3′UTR SNPs, which together could be arranged into eight distinct haplotypes based on expectation-maximization studies, with four predominant haplotypes (UTRs1-4). After HSCT, we found a moderate though not significant association between the presence of UTR-2 in double dose and protection from acute graft versus host disease (hazard ratio (HR) 0.45, 95% confidence intervals (CI): 0.14-1.45; P = 0.18), an effect that was also seen when the corresponding 14 bp ins/ins genotype was considered alone (HR 0.42, 95% CI: 0.16-1.06; P = 0.07). No association was found with rejection or survival. Taken together, our data show that there is no apparent added value of considering entire 3′UTR HLA-G haplotypes for risk prediction after allogeneic HSCT for beta-thalassemia.

KW - 3′ untranslated region

KW - Genotypes

KW - Haplotypes

KW - Hematopoietic stem cell transplantation

KW - Human leukocyte antigen-G

KW - Polymorphisms

KW - Population studies

KW - Thalassemia

UR - http://www.scopus.com/inward/record.url?scp=84859583274&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859583274&partnerID=8YFLogxK

U2 - 10.1111/j.1399-0039.2012.01862.x

DO - 10.1111/j.1399-0039.2012.01862.x

M3 - Article

C2 - 22489942

AN - SCOPUS:84859583274

VL - 79

SP - 326

EP - 332

JO - Tissue Antigens

JF - Tissue Antigens

SN - 0001-2815

IS - 5

ER -