CTLA-4 gene polymorphisms predispose to autoimmune endocrinopathies but not to celiac disease.
OBJECTIVE
The aim of the study was to determine the association of two CTLA-4 gene polymorphisms (CT60, +49 A/G) with Hashimoto thyroiditis (HT), type 1 diabetes mellitus (T1DM) and celiac disease (CD) as well as with the occurrence of multi-organ involvement by autoimmunity in children.


METHODS
Genotyping was done by RFLP analysis in Slovak children with HT (n=63) and CD (n=120) and both Slovak and Slovene children with T1DM (n=320) and healthy controls (n=231).


RESULTS
We found a significant association of the G allele of the CT60 polymorphism with HT (p<0,0005) in the Slovak population and T1DM in both Slovak (p<0.01) and Slovene populations (p<0.005). The G allele of the +49A/G polymorphism was significantly, though less strongly, associated with T1DM (p<0.05) and HT (p<0.05). Distribution of genotypes of CTLA-4 gene polymorphisms in CD patients did not differ significantly from controls. None of the polymorphisms was associated with multi-organ involvement by autoimmunity.


CONCLUSIONS
The G allele of both examined CTLA-4 gene polymorphisms predisposes to HT and T1DM, but not to CD. No association with multi-organ involvement was found. The GG genotype of the CT60 polymorphism may identify CD patients at an increased risk for concomitant T1DM and HT. Further studies to assess the predictive value of CTLA-4 polymorphisms for the co-occurrence of HT and T1DM in CD patients are needed.
Dallos
Tomás
T
2nd Department of Pediatrics, Medical Faculty, Comenius University, Limbová 1, 83340 Bratislava, Slovakia. dallos@dfnsp.sk
Avbelj
Magdalena
M
Barák
L'ubomír
L
Zapletalová
Jirina
J
Pribilincová
Zuzana
Z
Krajcírová
Mária
M
Kostálová
L'udmila
L
Battelino
Tadej
T
Kovács
László
L
D000293:Adolescent; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D001327:Autoimmune Diseases / Q000453:epidemiology* / Q000235:genetics*; D060908:CTLA-4 Antigen; D002446:Celiac Disease / Q000453:epidemiology* / Q000235:genetics*; D002648:Child; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000235:genetics; D004700:Endocrine System Diseases / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018154:Slovakia / Q000453:epidemiology; D017524:Slovenia / Q000453:epidemiology
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D005819:Genetic Markers