Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families

M. Schmitt-Egenolf, C. Windemuth, H. C. Hennies, M. Albis-Camps, B. Von Engelhardt, T. Wienker, A. Reis, H. Traupe, R. Blasczyk

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

LanguageEnglish
Pages440-446
Number of pages7
JournalTissue Antigens
Volume57
Issue number5
DOIs
Publication statusPublished - 9 Jul 2001
Externally publishedYes

Fingerprint

Psoriasis
Haplotypes
HLA-C Antigens
HLA Antigens
Polymorphism
Alleles
Nucleotides
Genes
Major Histocompatibility Complex
Nuclear Family
Keratinocytes
Single Nucleotide Polymorphism
Joints
HLA-C*06 antigen
Population

Cite this

Schmitt-Egenolf, M. ; Windemuth, C. ; Hennies, H. C. ; Albis-Camps, M. ; Von Engelhardt, B. ; Wienker, T. ; Reis, A. ; Traupe, H. ; Blasczyk, R. / Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families. In: Tissue Antigens. 2001 ; Vol. 57, No. 5. pp. 440-446.
@article{3ead6029083747c58d36ebd5e3aeb424,
title = "Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families",
abstract = "HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).",
keywords = "Autoimmune disease, Disease-susceptibility, Genetic markers, Genetics, Hereditary diseases, Histocompatibility antigens",
author = "M. Schmitt-Egenolf and C. Windemuth and Hennies, {H. C.} and M. Albis-Camps and {Von Engelhardt}, B. and T. Wienker and A. Reis and H. Traupe and R. Blasczyk",
year = "2001",
month = "7",
day = "9",
doi = "10.1034/j.1399-0039.2001.057005440.x",
language = "English",
volume = "57",
pages = "440--446",
journal = "HLA",
issn = "2059-2302",
publisher = "Wiley-Blackwell",
number = "5",

}

Schmitt-Egenolf, M, Windemuth, C, Hennies, HC, Albis-Camps, M, Von Engelhardt, B, Wienker, T, Reis, A, Traupe, H & Blasczyk, R 2001, 'Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families', Tissue Antigens, vol. 57, no. 5, pp. 440-446. https://doi.org/10.1034/j.1399-0039.2001.057005440.x

Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families. / Schmitt-Egenolf, M.; Windemuth, C.; Hennies, H. C.; Albis-Camps, M.; Von Engelhardt, B.; Wienker, T.; Reis, A.; Traupe, H.; Blasczyk, R.

In: Tissue Antigens, Vol. 57, No. 5, 09.07.2001, p. 440-446.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Comparative association analysis reveals that corneodesmosin is more closely associated with psoriasis than HLA-Cw*0602-B*5701 in German families

AU - Schmitt-Egenolf, M.

AU - Windemuth, C.

AU - Hennies, H. C.

AU - Albis-Camps, M.

AU - Von Engelhardt, B.

AU - Wienker, T.

AU - Reis, A.

AU - Traupe, H.

AU - Blasczyk, R.

PY - 2001/7/9

Y1 - 2001/7/9

N2 - HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

AB - HLA antigens are associated with psoriasis vulgaris across populations with different ethnic background. We have previously shown that in Caucasians this association is primarily based on the class I alleles of the extended HLA haplotype 57.1 (EH57.1/I), HLA-Cw6-HLA-B57. However, it remained unclear whether HLA-Cw6 itself or a closely linked locus predisposes to the disease. An interesting candidate for this presumed locus is corneodesmosin, which is exclusively synthesized in keratinocytes. The corneodesmosin gene locus (CDSN) is only 160 kb telomeric to HLA-C and tightly associated with psoriasis. In order to find out whether EH57.1/I or a corneodesmosin variant are the susceptibility determinants on 6p, HLA class I alleles and single-nucleotide polymorphisms (SNPs) of corneodesmosin were investigated at the sequence level and analyzed by comparative association tests. Transmission disequilibrium tests (TDT) were performed in 52 nuclear families, of which 36 were fully informative for a joint comparison of HLA and CDSN with regard to association to psoriasis. The extended TDT according to Wilson was employed to test for locus interaction. Using the HLA haplotype EH57.1/I and the CDSN haplotype formed by three intragenic variant sites at nt=619 (T), 1236 (T), and 1243 (C), we obtained the best resolution of parental transmission to index cases in the trio families. On direct comparison of the contributions of the HLA and the CDSN haplotypes, there was a markedly stronger association of the corneodesmosin TTC haplotype, which is not apparent in single locus analysis. We show furthermore that there is no higher order interaction between psoriasis, HLA, and CDSN. This lack of three-locus interaction is suggestive of two independent genetic contributions to psoriasis within the major histocompatibility complex (MHC).

KW - Autoimmune disease

KW - Disease-susceptibility

KW - Genetic markers

KW - Genetics

KW - Hereditary diseases

KW - Histocompatibility antigens

UR - http://www.scopus.com/inward/record.url?scp=0034960615&partnerID=8YFLogxK

U2 - 10.1034/j.1399-0039.2001.057005440.x

DO - 10.1034/j.1399-0039.2001.057005440.x

M3 - Article

VL - 57

SP - 440

EP - 446

JO - HLA

T2 - HLA

JF - HLA

SN - 2059-2302

IS - 5

ER -