HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus

L. Esposito, V. Lampasona, E. Bosi, F. Poli, M. Ferrari, E. Bonifacio

Research output: Contribution to journalArticle

Abstract

The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc-8) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.

Original languageEnglish
Pages (from-to)968-974
Number of pages7
JournalDiabetologia
Volume38
Issue number8
DOIs
Publication statusPublished - Aug 1995

Fingerprint

Type 1 Diabetes Mellitus
Haplotypes
Gene Frequency
HLA-DQ Antigens
HLA-DQA1 antigen
HLA-DQB1 antigen
Linkage Disequilibrium
Antigen Presentation
Insulin

Keywords

  • Antigen presentation
  • HLA class II
  • insulin-dependent diabetes mellitus
  • linkage disequilibrium
  • TAP peptide transporter gene

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

HLA DQA1-DQB1-TAP2 haplotypes in IDDM families : no evidence for an additional contribution to disease risk by the TAP2 locus. / Esposito, L.; Lampasona, V.; Bosi, E.; Poli, F.; Ferrari, M.; Bonifacio, E.

In: Diabetologia, Vol. 38, No. 8, 08.1995, p. 968-974.

Research output: Contribution to journalArticle

@article{99245bbf20e243cba4fbd454b6f8593e,
title = "HLA DQA1-DQB1-TAP2 haplotypes in IDDM families: no evidence for an additional contribution to disease risk by the TAP2 locus",
abstract = "The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28{\%} in control subjects, pc-8) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4{\%}) similar to that in IDDM haplotypes. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.",
keywords = "Antigen presentation, HLA class II, insulin-dependent diabetes mellitus, linkage disequilibrium, TAP peptide transporter gene",
author = "L. Esposito and V. Lampasona and E. Bosi and F. Poli and M. Ferrari and E. Bonifacio",
year = "1995",
month = "8",
doi = "10.1007/BF00400587",
language = "English",
volume = "38",
pages = "968--974",
journal = "Diabetologia",
issn = "0012-186X",
publisher = "Springer Verlag",
number = "8",

}

TY - JOUR

T1 - HLA DQA1-DQB1-TAP2 haplotypes in IDDM families

T2 - no evidence for an additional contribution to disease risk by the TAP2 locus

AU - Esposito, L.

AU - Lampasona, V.

AU - Bosi, E.

AU - Poli, F.

AU - Ferrari, M.

AU - Bonifacio, E.

PY - 1995/8

Y1 - 1995/8

N2 - The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc-8) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.

AB - The TAP2 gene, located in the HLA class II region, encodes a subunit of a transporter involved in the endogenous antigen-processing pathway, and has been suggested to contribute to the genetic risk for insulin-dependent diabetes (IDDM). In order to determine whether the TAP2 locus modulates the risk conferred by HLA DQ loci, HLA DQA1-DQB1-TAP2 haplotypes were analysed in 48 IDDM probands, their first degree relatives, and in 62 normal control subjects. A decreased frequency of the TAP2B allele was confirmed in this IDDM cohort (12 vs 28% in control subjects, pc-8) indicating strong linkage between these loci. Family haplotype analysis demonstrated linkage disequilibrium between TAP2 and HLA DQA1-DQB1, and showed that the reduced frequency of TAP2B was associated with its absence on the IDDM susceptible DQA1*0301-DQB1*0302 haplotype, its low frequency on DQA1*0501-DQB1*0201, and the association of TAP2B with DQA1*0101-DQB1*0501 haplotypes which were less frequent in IDDM patients. Comparison of transmitted with non-transmitted haplotypes in IDDM families showed a slight but not significant decrease in TAP2B allele frequency on transmitted (3 of 37) vs non-transmitted (2 of 9) HLA DQA1*0501-DQB1*0201 haplotypes. No other differences were observed. Twenty-four unrelated DQA1*0501-DQB1*0201 haplotypes from non-diabetic families had a TAP2B allele frequency (4%) similar to that in IDDM haplotypes. These findings suggest that the decreased TAP2B allele frequency in Italian IDDM patients is due to HLA DQ haplotype differences between IDDM patients and control subjects, and do not support a contribution to IDDM risk by the TAP2 locus.

KW - Antigen presentation

KW - HLA class II

KW - insulin-dependent diabetes mellitus

KW - linkage disequilibrium

KW - TAP peptide transporter gene

UR - http://www.scopus.com/inward/record.url?scp=0029101318&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029101318&partnerID=8YFLogxK

U2 - 10.1007/BF00400587

DO - 10.1007/BF00400587

M3 - Article

C2 - 7589884

AN - SCOPUS:0029101318

VL - 38

SP - 968

EP - 974

JO - Diabetologia

JF - Diabetologia

SN - 0012-186X

IS - 8

ER -