Abstract
Variation in clinical phenotype is a hallmark of many complex diseases. The cause of this clinical heterogeneity is unknown, but it may be determined by genetic factors distinct from those conferring disease susceptibility. Common variable immunodeficiency (CVID) is a complex disease of unknown aetiology and diverse clinical manifestations. We have developed a unified polymerase chain reaction and sequence-specific primer (PCR-SSP) method to simultaneously genotype multiple polymorphisms under identical conditions, and have used this method to test the hypothesis that the clinical phenotype of CVID is determined by immunoregulatory gene polymorphism. Twenty-three polymorphisms in 13 genes were studied in 163 CVID patients. Vitamin D receptor and IL-6 alleles were associated with immunophenotypic abnormalities characteristic of more severe disease; and tumour necrosis factor and IL-10 alleles conferred susceptibility to the granulomatous form of CVID in an interacting fashion. These findings demonstrate that different clinical features of a disease may have unique pathogenetic abnormalities, determined by multiple interacting genetic factors. The ease of application of this efficient, robust genotyping technique to polymorphisms throughout the genome will make it a powerful tool in the investigation of the genetic basis of phenotypic variability in a wide variety of diseases.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 6 digital issues and online access to articles
$119.00 per year
only $19.83 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Mullighan, C., Marshall, S., Bunce, M. et al. Variation in immunoregulatory genes determines the clinical phenotype of common variable immunodeficiency. Genes Immun 1, 137–148 (1999). https://doi.org/10.1038/sj.gene.6363653
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/sj.gene.6363653
Keywords
This article is cited by
-
Immunopathogenesis of granulomas in chronic autoinflammatory diseases
Clinical & Translational Immunology (2016)
-
CT Screening for Pulmonary Pathology in Common Variable Immunodeficiency Disorders and the Correlation with Clinical and Immunological Parameters
Journal of Clinical Immunology (2014)
-
Rapid and Simultaneous Detection of Vitamin D Receptor Gene Polymorphisms by a Single ARMS-PCR Assay
Molecular Diagnosis & Therapy (2014)
-
Combined effect of pro- and anti-inflammatory cytokine gene polymorphisms on susceptibility to liver cirrhosis in Tunisian HCV-infected patients
Hepatology International (2011)
-
Common variable immune deficiency: reviews, continued puzzles, and a new registry
Immunologic Research (2007)