Relationship between copy number of genes (C4A, C4B) encoding the fourth component of complement and the clinical course of hereditary angioedema (HAE)

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

In order to study if in patients with hereditary angioedema (HAE), copy number of the two genes (C4A and C4A) encoded in the central region of main histocompatibility complex (MHC) influences the diagnostically important C4 serum concentration as well as the clinical course of the disease, we determined copy number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and 246 healthy controls. Distribution of both the C4A and C4B copy numbers significantly (p = 0.0183 and 0.0318, respectively) differed between the two groups, the most marked difference we observed was the lower frequency of the high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of both C4A and C4B genes positively correlated to the longitudinally measured serum C4 concentrations. Moreover, we found an unexpected clinical correlation with the dosage of the C4B gene. The course of the disease was milder in the 9/95 patients carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e. diagnosis was established at significantly (p = 0.0052) older age (36.0 (31.0-39.5)) years versus 20.5 (7.5-31.5 years), biyearly attack rate was significantly (p = 0.0145) lower (1.0 (0.0-11.0)) versus 11.0 (3.5-21.5), and the over-all activity of the classical pathway and the enzyme-inhibitor activity of the C1-inhibitor (C1-INH) was closer to the normal values. These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.

Original languageEnglish
Pages (from-to)2667-2674
Number of pages8
JournalMolecular Immunology
Volume44
Issue number10
DOIs
Publication statusPublished - Apr 2007

Fingerprint

Hereditary Angioedemas
Gene Dosage
Genes
Enzyme Inhibitors
Major Histocompatibility Complex
Serum
Reference Values
DNA

Keywords

  • Complement C4
  • Copy number polymorphism
  • Copy number variation
  • HAE

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

@article{8c8cfda7c7654746a5684a3b0cd76403,
title = "Relationship between copy number of genes (C4A, C4B) encoding the fourth component of complement and the clinical course of hereditary angioedema (HAE)",
abstract = "In order to study if in patients with hereditary angioedema (HAE), copy number of the two genes (C4A and C4A) encoded in the central region of main histocompatibility complex (MHC) influences the diagnostically important C4 serum concentration as well as the clinical course of the disease, we determined copy number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and 246 healthy controls. Distribution of both the C4A and C4B copy numbers significantly (p = 0.0183 and 0.0318, respectively) differed between the two groups, the most marked difference we observed was the lower frequency of the high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of both C4A and C4B genes positively correlated to the longitudinally measured serum C4 concentrations. Moreover, we found an unexpected clinical correlation with the dosage of the C4B gene. The course of the disease was milder in the 9/95 patients carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e. diagnosis was established at significantly (p = 0.0052) older age (36.0 (31.0-39.5)) years versus 20.5 (7.5-31.5 years), biyearly attack rate was significantly (p = 0.0145) lower (1.0 (0.0-11.0)) versus 11.0 (3.5-21.5), and the over-all activity of the classical pathway and the enzyme-inhibitor activity of the C1-inhibitor (C1-INH) was closer to the normal values. These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.",
keywords = "Complement C4, Copy number polymorphism, Copy number variation, HAE",
author = "B. Blask{\'o} and G. Sz{\'e}plaki and L. Varga and Z. R{\'o}nai and Z. Proh{\'a}szka and M. Sasv{\'a}ri and B. Visy and H. Farkas and G. F{\"u}st",
year = "2007",
month = "4",
doi = "10.1016/j.molimm.2006.12.007",
language = "English",
volume = "44",
pages = "2667--2674",
journal = "Molecular Immunology",
issn = "0161-5890",
publisher = "Elsevier Limited",
number = "10",

}

TY - JOUR

T1 - Relationship between copy number of genes (C4A, C4B) encoding the fourth component of complement and the clinical course of hereditary angioedema (HAE)

AU - Blaskó, B.

AU - Széplaki, G.

AU - Varga, L.

AU - Rónai, Z.

AU - Prohászka, Z.

AU - Sasvári, M.

AU - Visy, B.

AU - Farkas, H.

AU - Füst, G.

PY - 2007/4

Y1 - 2007/4

N2 - In order to study if in patients with hereditary angioedema (HAE), copy number of the two genes (C4A and C4A) encoded in the central region of main histocompatibility complex (MHC) influences the diagnostically important C4 serum concentration as well as the clinical course of the disease, we determined copy number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and 246 healthy controls. Distribution of both the C4A and C4B copy numbers significantly (p = 0.0183 and 0.0318, respectively) differed between the two groups, the most marked difference we observed was the lower frequency of the high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of both C4A and C4B genes positively correlated to the longitudinally measured serum C4 concentrations. Moreover, we found an unexpected clinical correlation with the dosage of the C4B gene. The course of the disease was milder in the 9/95 patients carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e. diagnosis was established at significantly (p = 0.0052) older age (36.0 (31.0-39.5)) years versus 20.5 (7.5-31.5 years), biyearly attack rate was significantly (p = 0.0145) lower (1.0 (0.0-11.0)) versus 11.0 (3.5-21.5), and the over-all activity of the classical pathway and the enzyme-inhibitor activity of the C1-inhibitor (C1-INH) was closer to the normal values. These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.

AB - In order to study if in patients with hereditary angioedema (HAE), copy number of the two genes (C4A and C4A) encoded in the central region of main histocompatibility complex (MHC) influences the diagnostically important C4 serum concentration as well as the clinical course of the disease, we determined copy number of the complement C4A and C4B genes in DNA samples of 95 HAE patients and 246 healthy controls. Distribution of both the C4A and C4B copy numbers significantly (p = 0.0183 and 0.0318, respectively) differed between the two groups, the most marked difference we observed was the lower frequency of the high (3 or 4) C4A copy numbers in the patients. As it expected, the dosage of both C4A and C4B genes positively correlated to the longitudinally measured serum C4 concentrations. Moreover, we found an unexpected clinical correlation with the dosage of the C4B gene. The course of the disease was milder in the 9/95 patients carrying 3 or 4 copies of C4B gene, compared to the rest of patients, i.e. diagnosis was established at significantly (p = 0.0052) older age (36.0 (31.0-39.5)) years versus 20.5 (7.5-31.5 years), biyearly attack rate was significantly (p = 0.0145) lower (1.0 (0.0-11.0)) versus 11.0 (3.5-21.5), and the over-all activity of the classical pathway and the enzyme-inhibitor activity of the C1-inhibitor (C1-INH) was closer to the normal values. These observations indicate that high copy number of the C4B gene can be a protective factor against disease severity in HAE and therefore its determination is warranted.

KW - Complement C4

KW - Copy number polymorphism

KW - Copy number variation

KW - HAE

UR - http://www.scopus.com/inward/record.url?scp=33846927763&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846927763&partnerID=8YFLogxK

U2 - 10.1016/j.molimm.2006.12.007

DO - 10.1016/j.molimm.2006.12.007

M3 - Article

VL - 44

SP - 2667

EP - 2674

JO - Molecular Immunology

JF - Molecular Immunology

SN - 0161-5890

IS - 10

ER -