A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis

V. Brazzelli, M. Quaglini, M. Martinetti, G. Nolli, L. Salvaneschi, M. Cuccia, Giovanni Borroni

Research output: Contribution to journalArticle

Abstract

Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ2 = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α1-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ2 = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ2 = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future. Copyright (C) 2000 S. Karger AG, Basel.

Original languageEnglish
Pages (from-to)99-103
Number of pages5
JournalDermatology
Volume200
Issue number2
Publication statusPublished - 2000

Fingerprint

HLA-C Antigens
Psoriasis
Immunogenetics
Amino Acid Substitution
Gene Frequency
Italy
Genes
Amino Acid Sequence
Exons
Antigens
Amino Acids
Polymerase Chain Reaction
Peptides
Population

Keywords

  • α-domain
  • HLA-C sequence motif
  • Psoriasis

ASJC Scopus subject areas

  • Dermatology

Cite this

Brazzelli, V., Quaglini, M., Martinetti, M., Nolli, G., Salvaneschi, L., Cuccia, M., & Borroni, G. (2000). A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis. Dermatology, 200(2), 99-103.

A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis. / Brazzelli, V.; Quaglini, M.; Martinetti, M.; Nolli, G.; Salvaneschi, L.; Cuccia, M.; Borroni, Giovanni.

In: Dermatology, Vol. 200, No. 2, 2000, p. 99-103.

Research output: Contribution to journalArticle

Brazzelli, V, Quaglini, M, Martinetti, M, Nolli, G, Salvaneschi, L, Cuccia, M & Borroni, G 2000, 'A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis', Dermatology, vol. 200, no. 2, pp. 99-103.
Brazzelli V, Quaglini M, Martinetti M, Nolli G, Salvaneschi L, Cuccia M et al. A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis. Dermatology. 2000;200(2):99-103.
Brazzelli, V. ; Quaglini, M. ; Martinetti, M. ; Nolli, G. ; Salvaneschi, L. ; Cuccia, M. ; Borroni, Giovanni. / A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis. In: Dermatology. 2000 ; Vol. 200, No. 2. pp. 99-103.
@article{8741283d85e34c378f844d97bb045df6,
title = "A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis",
abstract = "Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6{\%}, χ2 = 14.65, p = 0.000129). This frequency rose to 39.5{\%} in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α1-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5{\%} of the cases against the 50.82{\%} of controls (χ2 = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15{\%} of patients and in 0{\%} of controls (χ2 = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future. Copyright (C) 2000 S. Karger AG, Basel.",
keywords = "α-domain, HLA-C sequence motif, Psoriasis",
author = "V. Brazzelli and M. Quaglini and M. Martinetti and G. Nolli and L. Salvaneschi and M. Cuccia and Giovanni Borroni",
year = "2000",
language = "English",
volume = "200",
pages = "99--103",
journal = "Dermatology",
issn = "1018-8665",
publisher = "S. Karger AG",
number = "2",

}

TY - JOUR

T1 - A peculiar sequence motif in the alpha-1-domain of the HLA-C molecule in psoriasis

AU - Brazzelli, V.

AU - Quaglini, M.

AU - Martinetti, M.

AU - Nolli, G.

AU - Salvaneschi, L.

AU - Cuccia, M.

AU - Borroni, Giovanni

PY - 2000

Y1 - 2000

N2 - Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ2 = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α1-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ2 = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ2 = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future. Copyright (C) 2000 S. Karger AG, Basel.

AB - Background: Most immunogenetic studies restrict the location of the susceptibility gene for psoriasis to the HLA-C locus. Objective: The present study evaluates the amino acid sequences of the HLA-C binding groove associated with the disease in a restricted population of Italian descent: Pavia, Northern Italy. Method: Forty patients, affected by psoriasis, underwent genomic analysis of exons 2 and 3 of the HLA-C gene by means of the PCR-SSP technique. Results: The HLA-C*0602 gene frequency was significantly higher in patients with respect to 122 sex-, age- and ethnically matched controls (25 vs. 8.6%, χ2 = 14.65, p = 0.000129). This frequency rose to 39.5% in patients with a family history positive for psoriasis. In particular, 4 amino acid substitutions were shown to be crucial for the predisposition to the disease, namely Ala 73 and Asn 77 (located in the C pocket of the antigen binding groove), Lys 80 in the F pocket and Asp 90 in the outer loop of the molecule. This peculiar motif, entirely located in the α1-domain of the HLA-C molecule, was characteristic of psoriatic patients being present in 77.5% of the cases against the 50.82% of controls (χ2 = 8.77; p = 0.0031). Homozygosity for the amino acids considered at these residues was found in 15% of patients and in 0% of controls (χ2 = 20.74, p = 0.0000053). Conclusion: The most important results emerging from this study indicate that Ala 73, Asn 77, Lys 80 and Asp 90 together form a motif restricted to few pathogenic peptides to be studied in the near future. Copyright (C) 2000 S. Karger AG, Basel.

KW - α-domain

KW - HLA-C sequence motif

KW - Psoriasis

UR - http://www.scopus.com/inward/record.url?scp=0034037768&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034037768&partnerID=8YFLogxK

M3 - Article

C2 - 10773694

AN - SCOPUS:0034037768

VL - 200

SP - 99

EP - 103

JO - Dermatology

JF - Dermatology

SN - 1018-8665

IS - 2

ER -