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Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis

Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis
Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis

The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.

Case-Control Studies, Chromosomes, Human, Pair 6, Cryoglobulinemia, Cryoglobulins, Female, Genes, MHC Class II, Genome-Wide Association Study, Hepatitis C, Humans, Male, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Receptors, Notch, Vasculitis, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
1466-4879
500-5
Zignego, A L
8914d7a9-8fbc-475f-bbc5-35364f0beebb
Wojcik, G L
655b60f1-1341-45d5-8dc6-450a6e946654
Cacoub, P
5ebee8fe-eff4-4bf9-8f1c-8802aaacfaff
Visentini, M
c9627e99-6166-431b-ab93-41bc862b1ecd
Casato, M
b6cd7bc3-d583-4d29-a9af-3374454f8c33
Mangia, A
6df38d2d-64c8-4147-bff2-b00eafb36ec7
Latanich, R
6ecc5f95-ee38-4dab-a438-3cfa03c87df4
Charles, E D
352f146e-32b7-44f2-8b6b-c2f5bfe5d402
Gragnani, L
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Terrier, B
6df7cfc0-8c51-4ac6-845f-f0748663e2c8
Piazzola, V
cc4e7aac-c328-4562-a196-427a5430aa6b
Dustin, L B
219f9994-701f-419d-a20d-20b93a359cda
Khakoo, S I
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Busch, M P
684ff0d7-5fa0-42f4-af0b-4320f5bc445f
Lauer, G M
6b956e02-9d48-4281-a829-80d82fcc1c79
Kim, A Y
1feca326-166e-448e-9f48-88c49a68726d
Alric, L
bfa2cfb1-b0a4-41df-a9d9-76a55a02c8ec
Thomas, D L
997c78e0-3849-4ce8-b1bc-86ebbdee3953
Duggal, P
01046bda-6bcc-4c62-9e34-4921765fabcf
Zignego, A L
8914d7a9-8fbc-475f-bbc5-35364f0beebb
Wojcik, G L
655b60f1-1341-45d5-8dc6-450a6e946654
Cacoub, P
5ebee8fe-eff4-4bf9-8f1c-8802aaacfaff
Visentini, M
c9627e99-6166-431b-ab93-41bc862b1ecd
Casato, M
b6cd7bc3-d583-4d29-a9af-3374454f8c33
Mangia, A
6df38d2d-64c8-4147-bff2-b00eafb36ec7
Latanich, R
6ecc5f95-ee38-4dab-a438-3cfa03c87df4
Charles, E D
352f146e-32b7-44f2-8b6b-c2f5bfe5d402
Gragnani, L
7e6b68bc-a2ae-4557-8911-e6b4b943cd2f
Terrier, B
6df7cfc0-8c51-4ac6-845f-f0748663e2c8
Piazzola, V
cc4e7aac-c328-4562-a196-427a5430aa6b
Dustin, L B
219f9994-701f-419d-a20d-20b93a359cda
Khakoo, S I
6c16d2f5-ae80-4d9b-9100-6bfb34ad0273
Busch, M P
684ff0d7-5fa0-42f4-af0b-4320f5bc445f
Lauer, G M
6b956e02-9d48-4281-a829-80d82fcc1c79
Kim, A Y
1feca326-166e-448e-9f48-88c49a68726d
Alric, L
bfa2cfb1-b0a4-41df-a9d9-76a55a02c8ec
Thomas, D L
997c78e0-3849-4ce8-b1bc-86ebbdee3953
Duggal, P
01046bda-6bcc-4c62-9e34-4921765fabcf

Zignego, A L, Wojcik, G L, Cacoub, P, Visentini, M, Casato, M, Mangia, A, Latanich, R, Charles, E D, Gragnani, L, Terrier, B, Piazzola, V, Dustin, L B, Khakoo, S I, Busch, M P, Lauer, G M, Kim, A Y, Alric, L, Thomas, D L and Duggal, P (2014) Genome-wide association study of hepatitis C virus- and cryoglobulin-related vasculitis. Genes and Immunity, 15 (7), 500-5. (doi:10.1038/gene.2014.41).

Record type: Article

Abstract

The host genetic basis of mixed cryoglobulin vasculitis is not well understood and has not been studied in large cohorts. A genome-wide association study was conducted among 356 hepatitis C virus (HCV) RNA-positive individuals with cryoglobulin-related vasculitis and 447 ethnically matched, HCV RNA-positive controls. All cases had both serum cryoglobulins and a vasculitis syndrome. A total of 899 641 markers from the Illumina HumanOmni1-Quad chip were analyzed using logistic regression adjusted for sex, as well as genetically determined ancestry. Replication of select single-nucleotide polymorphisms (SNPs) was conducted using 91 cases and 180 controls, adjusting for sex and country of origin. The most significant associations were identified on chromosome 6 near the NOTCH4 and MHC class II genes. A genome-wide significant association was detected on chromosome 6 at SNP rs9461776 (odds ratio=2.16, P=1.16E-07) between HLA-DRB1 and DQA1: this association was further replicated in additional independent samples (meta-analysis P=7.1 × 10(-9)). A genome-wide significant association with cryoglobulin-related vasculitis was identified with SNPs near NOTCH4 and MHC Class II genes. The two regions are correlated and it is difficult to disentangle which gene is responsible for the association with mixed cryoglobulinemia vasculitis in this extended major histocompatibility complex region.

Full text not available from this repository.

More information

Published date: October 2014
Keywords: Case-Control Studies, Chromosomes, Human, Pair 6, Cryoglobulinemia, Cryoglobulins, Female, Genes, MHC Class II, Genome-Wide Association Study, Hepatitis C, Humans, Male, Polymorphism, Single Nucleotide, Proto-Oncogene Proteins, Receptors, Notch, Vasculitis, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't
Organisations: University of Southampton

Identifiers

Local EPrints ID: 409577
URI: http://eprints.soton.ac.uk/id/eprint/409577
ISSN: 1466-4879
PURE UUID: 4d93f2a0-e2a3-4769-af9f-09b57f3ce793

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Date deposited: 31 May 2017 04:00
Last modified: 13 Mar 2019 19:51

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Contributors

Author: A L Zignego
Author: G L Wojcik
Author: P Cacoub
Author: M Visentini
Author: M Casato
Author: A Mangia
Author: R Latanich
Author: E D Charles
Author: L Gragnani
Author: B Terrier
Author: V Piazzola
Author: L B Dustin
Author: S I Khakoo
Author: M P Busch
Author: G M Lauer
Author: A Y Kim
Author: L Alric
Author: D L Thomas
Author: P Duggal

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