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Association of Hashimoto's thyroiditis with cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and inducible co-stimulator (ICOS) genes in a Kuwaiti population.
MedLine Citation:
PMID:  23138463     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Analysing two CTLA-4 markers [exon 1 A49G single nucleotide polymorphism (SNP) and exon 4 3'UTR (AT)n repeat] and the ICOS intron 4 (GT)n marker for their potential association with HT, and exploring the effect of the tested SNPs on the CTLA-4 isoform expression at the mRNA and protein levels. Total of 270 age-gender-ethnically matched subjects were genotyped by fluorescent-labelled restriction fragment length polymorphism, multiplex PCR, and fragment analysis. Sequencing was used to confirm the genotyping results. Expression of the full-length and soluble CTLA-4 mRNAs analysed using real-time PCR. Sera from subjects were screened for sCTLA-4 using ELISA. Tested subjects revealed ten alleles and sixteen genotypes of CTLA-4 3'UTR(AT)n. The 3'UTR(AT)n was significantly associated with HT: allele (AT)15 and genotype 15/15 were found to cause susceptibility to HT (P = 0.004, OR = 2.13, 95 % CI = 1.26-3.58 and P = 0.029, OR = 2.77, 95 % CI = 1.1-6.94, respectively), whereas allele (AT)6 and genotype 6/6 were found to be protective of HT (P = 0.00002, OR = 0.36, 95 % CI = 0.227-0.57 and P = 0.001, OR = 0.357, 95 % CI = 0.1980.64, respectively). SNP A49G and ICOS(GT)n revealed no significant association with HT (P > 0.05). The expression of sCTLA-4 was inversely proportional to the number of 3'UTR(AT)n repeats, with heterozygous and longer (AT)n repeats showing lower levels of sCTLA-4 mRNA than those with shorter alleles in HC and HT (P = 0.001 and P = 0.04, respectively). Significant increase in the serum level of sCTLA-4 was observed in HT patients compared with the HC (P = 0.0007). The novel finding in our study is that the CTLA-4 3'UTR(AT)n proven to be a key player in the pathogenesis of HT.
Authors:
Suad Alfadhli; Qamar Almutawa; Jasem M K Abbas; Suhail A R Doi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-11-9
Journal Detail:
Title:  Endocrine     Volume:  -     ISSN:  1559-0100     ISO Abbreviation:  Endocrine     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-11-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9434444     Medline TA:  Endocrine     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Medical Laboratory Sciences, Faculty of Allied Health Sciences, Kuwait University, P.O. Box 31470, Sulaibekhat, Kuwait, s.alfadhli@hsc.edu.kw.
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