Open AccessAssociation analysis of PTPN22 , CTLA4 and IFIH1 genes with type 1 diabetes in C olombian families在哥伦比亚家族中进行的 PTPN22 、 CTLA4 以及 IFIH1 基因与1型糖尿病的相关性分析
Author(s) -
Rodríguez Alejandra,
Alfaro Juan Manuel,
Balthazar Vital,
Pineda Trujillo Nicolás
Publication year - 2015
Publication title -
journal of diabetes
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.949
H-Index - 43
eISSN - 1753-0407
pISSN - 1753-0393
DOI - 10.1111/1753-0407.12192
Subject(s) - ptpn22 , single nucleotide polymorphism , transmission disequilibrium test , population , allele , biology , microbiology and biotechnology , medicine , gene , genetics , genotype , environmental health
Background Protein tyrosine phosphatase, non‐receptor type 22 (lymphoid) ( PTPN22 ), cytotoxic T ‐lymphocyte‐associated protein 4 ( CTLA4 ), and interferon induced with helicase C domain 1 ( IFIH1 ) are among the confirmed type 1 diabetes ( T1D ) susceptibility genes in several populations. The aim of this study was to evaluate the role of PTPN22 , CTLA4 , and IFIH1 gene variants in the development of T1D in a C olombian population. Methods Associations of PTPN22 , CTLA4 , and IFIH1 variants with T1D were investigated in a sample of 197 nuclear families, including 205 affected children, in the C olombian population. Three to four single nucleotide polymorphisms ( SNP s) were analyzed per gene: rs2476600 , rs2476601 , rs1217418 , and rs2488457 for PTPN22 ; rs1990760 , rs3747517 , and rs10930046 for IFIH1 ; and rs231775 , rs3087243 , and rs231779 for CTLA4 . A transmission disequilibrium test was performed for the global sample, in addition to stratified analysis considering autoimmunity, age at onset, and parent of origin. Haplotypes per gene were also analyzed. Results There was no significant transmission distortion for CTLA4 . Conversely, SNPs rs10930046 ( IFIH1 ) and rs2476601 ( PTPN222 ) exhibited significant transmission distortion of the C and T alleles, respectively, from parents to affected children (odds ratio [ OR ] 0.57 and 1.83, respectively). In addition, decreased transmission of the C allele for rs10930046 occurred preferentially from mothers. Stratification analysis revealed that this association was maintained in individuals who were positive for autoantibodies and in those with an age of diagnosis <5 years. Conclusion The results show that IFIH1 and PTPN22 are associated with T1D in C olombian families.