CT60 and +49 polymorphisms of CTLA 4 are associated with ANCA-positive small vessel vasculitis.
OBJECTIVE
To investigate whether single nucleotide polymorphisms (SNPs) within cytotoxic T-lymphocyte antigen-4 (CTLA-4) are associated with ANCA-associated small vessel vasculitis (SVV).


METHODS
The CTLA-4 CT60 (exon 4), +49 (exon 1) and -318 (promoter region) genotypes were determined by PCR and restriction fragment length polymorphism (RFLP) in 222 white Caucasians of UK origin with SVV and 670 ethnically matched controls.


RESULTS
The CTLA-4 exon 1 (+49) and 4 (CT60) polymorphisms are associated with SVV (+49: chi(2) = 10.965, P = 0.004; CT60: chi(2) = 12.017, P = 0.002). Both disease-susceptible and disease-protective haplotypes have been identified in this cohort, and their frequencies are similar in the subtypes of WG and microscopic polyangiitis.


CONCLUSIONS
This study provides further evidence that CTLA-4, a susceptibility locus for a number of common autoimmune diseases, may also be involved in the development of ANCA-associated SVV.
Kamesh
Lavanya
L
Renal Unit, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Heward
Joanne M
JM
Williams
Julie M
JM
Gough
Stephen C L
SC
Chavele
Konstantia-Maria
KM
Salama
Alan
A
Pusey
Charles
C
Savage
Caroline O S
CO
Harper
Lorraine
L
D056648:Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis / Q000235:genetics* / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D020641:Polymorphism, Single Nucleotide
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human