The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T > C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Judit Laki, Petra Kiszel, Ágnes Vatay, B. Blaskó, M. Kovács, A. Körner, L. Madácsy, László Blatniczky, Zsuzsa Almássy, C. Szalai, K. Rajczy, Éva Pozsonyi, I. Karádi, Ádám Fazakas, N. Hosszúfalusi, P. Pánczél, Gudmundur J. Arason, Yee Ling Wu, Bi Zhou, Yan Yang & 2 others C. Yung Yu, G. Füst

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T > C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p <0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p = 0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

Original languageEnglish
Pages (from-to)648-655
Number of pages8
JournalMolecular Immunology
Volume44
Issue number4
DOIs
Publication statusPublished - Jan 2007

Fingerprint

Haplotypes
Alleles
Genes
Type 1 Diabetes Mellitus
Linkage Disequilibrium
Advanced Glycosylation End Product-Specific Receptor
MHC Class II Genes
Chromosomes, Human, Pair 6
HLA-DR Antigens
Population
Single Nucleotide Polymorphism
Genotype
Mothers
Mono-S

Keywords

  • 8.1 AH
  • Ancestral haplotype
  • Diabetes
  • Hemoglobin
  • RAGE

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

@article{9fb9f3f5a5cf4c6fb34318ad2bdb4b98,
title = "The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T > C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients",
abstract = "Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T > C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p <0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p = 0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.",
keywords = "8.1 AH, Ancestral haplotype, Diabetes, Hemoglobin, RAGE",
author = "Judit Laki and Petra Kiszel and {\'A}gnes Vatay and B. Blask{\'o} and M. Kov{\'a}cs and A. K{\"o}rner and L. Mad{\'a}csy and L{\'a}szl{\'o} Blatniczky and Zsuzsa Alm{\'a}ssy and C. Szalai and K. Rajczy and {\'E}va Pozsonyi and I. Kar{\'a}di and {\'A}d{\'a}m Fazakas and N. Hossz{\'u}falusi and P. P{\'a}ncz{\'e}l and Arason, {Gudmundur J.} and Wu, {Yee Ling} and Bi Zhou and Yan Yang and Yu, {C. Yung} and G. F{\"u}st",
year = "2007",
month = "1",
doi = "10.1016/j.molimm.2006.01.011",
language = "English",
volume = "44",
pages = "648--655",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T > C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

AU - Laki, Judit

AU - Kiszel, Petra

AU - Vatay, Ágnes

AU - Blaskó, B.

AU - Kovács, M.

AU - Körner, A.

AU - Madácsy, L.

AU - Blatniczky, László

AU - Almássy, Zsuzsa

AU - Szalai, C.

AU - Rajczy, K.

AU - Pozsonyi, Éva

AU - Karádi, I.

AU - Fazakas, Ádám

AU - Hosszúfalusi, N.

AU - Pánczél, P.

AU - Arason, Gudmundur J.

AU - Wu, Yee Ling

AU - Zhou, Bi

AU - Yang, Yan

AU - Yu, C. Yung

AU - Füst, G.

PY - 2007/1

Y1 - 2007/1

N2 - Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T > C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p <0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p = 0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

AB - Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T > C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p <0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p = 0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.

KW - 8.1 AH

KW - Ancestral haplotype

KW - Diabetes

KW - Hemoglobin

KW - RAGE

UR - http://www.scopus.com/inward/record.url?scp=33747843105&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747843105&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2006.01.011

DO - 10.1016/j.molimm.2006.01.011

M3 - Article

VL - 44

SP - 648

EP - 655

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 4

ER -