ASSOCIATION OF CTLA4 GENE WITH CELIAC DISEASE CONFIRMED IN CASE-CONTROL STUDIES AND TRANSMISSION DISEQUILIBRIUM TEST

Mlynarski W¹, Witas HW¹, Rujner J², Bodalski J¹

¹ Clinic of Paediatrics, Medical University of Łodz, Poland

² Department of Gastroenterology and Nutrition, Health Child Institute, Warsaw, Poland

Objective: To verify hypothesis assuming an association of CTLA4 gene, located within chromosome 2q34, with celiac disease in the Polish population.

Methods: Analysis of CTLA4 gene polymorphism within exon 1 (A®G transition, +49) was studied in 153 children with celiac disease (CD) and 223 healthy controls as well as in 32 families of CD patients (42 CD patients, 47 siblings, 63 parents). All studied subjects were of Polish origin. PCR followed by RFLP (ItaI) was applied to define alleles of the polymorphic site.

Results: Genotype GG was found more frequent in CD patients (19.6%) v. 7.6% controls (p=0.0026; RR=1.7, CI95%=1.43-1.98) as well G-alleles frequency was higher in CD (41.5 v. 33.4; p=0.03; RR=1.2, CI95%=1.09-1.35). That observation was also confirmed in transmission disequilibrium test (TDT). 34 of 63 parents were heterozygous for studied polymorphism. Thus, G-allele was transmitted in 28 of 42 CD patients (theoretically expected 22, p=0.03). This allele was transmitted in 21 of 47 healthy siblings.

Conclusion: Polymorphism of CTLA4 gene is associated with and probably, linked to celiac disease in Polish population.

The work was supported by KBN grant No 4 P05E 03618.

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