Variation in the CTLA4/CD28 gene region confers an increased risk of coeliac disease.

• Susceptibility to coeliac disease involves HLA and non-HLA-linked genes. The CTLA4/CD28 gene region encodes immune regulatory T-cell surface molecules and is a strong candidate as a susceptibility locus. We evaluated CTLA4/CD28 in coeliac disease by genetic linkage and association and combined our findings with published studies through a meta-analysis. 116 multiplex families were genotyped across CTLA4/CD28 using eight markers. The contribution of CTLA4/CD28 to coeliac disease was assessed by non-parametric linkage and association analyses. Seven studies were identified that had evaluated the relationship between CTLA4/CD28 and coeliac disease and a pooled analysis of data undertaken. In our study there was evidence for a relationship between variation in the CTLA4/CD28 region and coeliac disease by linkage and association analyses. However, the findings did not attain formal statistical significance (p = 0.004 and 0.039, respectively). Pooling findings with published results showed significant evidence for linkage (504 families) and association (940 families): p values, 0.0001 and 0.0014 at D2S2214, respectively, and 0.0008 and 0.0006 at D2S116, respectively. These findings suggest that variation in the CD28/CTLA4 gene region is a determinant of coeliac disease susceptibility. Dissecting the sequence variation underlying this relationship will depend on further analyses utilising denser sets of markers.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)

Nyckelord

Adolescent

Adult

Aged

Antigens

CD

Antigens

CD28

genetics

Antigens

Differentiation

genetics

Celiac Disease

epidemiology

genetics

immunology

Child

Child

Preschool

Chromosomes

Human

Pair 2

genetics

Europe

epidemiology

Female

Genetic Markers

Genetic Predisposition to Disease

Genotype

Humans

Immunoconjugates

Infant

Linkage (Genetics)

Male

Middle Aged

Risk

Statistics

Nonparametric

T-Lymphocytes

immunology

MEDICINE

Publikations- och innehållstyp

ref (ämneskategori)

art (ämneskategori)