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

2.50
Hdl Handle:
http://hdl.handle.net/2336/9827
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
Authors:
Laki, Judit; Kiszel, Petra; Vatay, Agnes; Blaskó, Bernadett; Kovács, Margit; Körner, Anna; Madácsy, László; Blatniczky, László; Almássy, Zsuzsa; Szalai, Csaba; Rajczy, Katalin; Pozsonyi, Eva; Karádi, István; Fazakas, Adám; Hosszúfalusi, Nóra; Pánczél, Pál; Arason, Gudmundur J; Wu, Yee-Ling; Zhou, Bi; Yang, Yan; Yu, C-Yung; Füst, George
Citation:
Mol. Immunol. 2007, 44(4):648-55
Issue Date:
1-Jan-2007
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.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://linkinghub.elsevier.com/retrieve/pii/S0161-5890(06)00021-6

Full metadata record

DC FieldValue Language
dc.contributor.authorLaki, Judit-
dc.contributor.authorKiszel, Petra-
dc.contributor.authorVatay, Agnes-
dc.contributor.authorBlaskó, Bernadett-
dc.contributor.authorKovács, Margit-
dc.contributor.authorKörner, Anna-
dc.contributor.authorMadácsy, László-
dc.contributor.authorBlatniczky, László-
dc.contributor.authorAlmássy, Zsuzsa-
dc.contributor.authorSzalai, Csaba-
dc.contributor.authorRajczy, Katalin-
dc.contributor.authorPozsonyi, Eva-
dc.contributor.authorKarádi, István-
dc.contributor.authorFazakas, Adám-
dc.contributor.authorHosszúfalusi, Nóra-
dc.contributor.authorPánczél, Pál-
dc.contributor.authorArason, Gudmundur J-
dc.contributor.authorWu, Yee-Ling-
dc.contributor.authorZhou, Bi-
dc.contributor.authorYang, Yan-
dc.contributor.authorYu, C-Yung-
dc.contributor.authorFüst, George-
dc.date.accessioned2007-03-07T09:13:34Z-
dc.date.available2007-03-07T09:13:34Z-
dc.date.issued2007-01-01-
dc.date.submitted2007-03-07-
dc.identifier.citationMol. Immunol. 2007, 44(4):648-55en
dc.identifier.issn0161-5890-
dc.identifier.pmid16504296-
dc.identifier.doi10.1016/j.molimm.2006.01.011-
dc.identifier.otherAAI12-
dc.identifier.urihttp://hdl.handle.net/2336/9827-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractPreviously 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.en
dc.language.isoenen
dc.publisherPergamon Pressen
dc.relation.urlhttp://linkinghub.elsevier.com/retrieve/pii/S0161-5890(06)00021-6en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAllelesen
dc.subject.meshChilden
dc.subject.meshDiabetes Mellitus, Type 1en
dc.subject.meshFemaleen
dc.subject.meshGene Frequencyen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshHLA Antigensen
dc.subject.meshHaplotypesen
dc.subject.meshHemoglobin A, Glycosylateden
dc.subject.meshHumansen
dc.subject.meshLinkage Disequilibriumen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPolymorphism, Single Nucleotideen
dc.subject.meshPromoter Regions (Genetics)en
dc.subject.meshReceptors, Immunologicen
dc.titleThe 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 patientsen
dc.typeArticleen
dc.identifier.journalMolecular Immunologyen
dc.format.digYES-

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