Here, we analysed the effect of T1D-associated major HLA class II haplotypes and seven single nucleotide polymorphisms in six non-HLA genes [INS (rs689), PTPN22 (rs2476601), IL2RA (rs12722495 and rs2104286), PTPN2 (rs45450798), CTLA4 (rs3087243) and ERBB3 (rs2292239)] on peripheral blood Treg frequencies.
Genetic polymorphisms (HLA haplotypes; rs231806, rs231775, and rs3087243 in CTLA4; rs763361 in CD226; and rs706778 in CD25) and T1D-associated autoantibodies were analyzed.
For the case-control studies, 1) the rs3087243 polymorphism was significantly associated with T1D [allele (fixed: odds ratio and 95% confidence interval (CI) = 1.249 (1.194-1.307), P < 0.001; random: odds ratio and 95%CI = 1.601 (1.103-2.325), P = 0.013)] [genotype (GG versus GA+AA: odds ratio and 95%CI = 1.249 (1.164-1.341), P < 0.001)], 2) there was no evidence to show that this association was accounted for in any study, and 3) there was no evidence for publication bias.
With respect to the rs3087243 (+6230G>A) polymorphism of CTLA4, the first sister had type 1 diabetes and AITD and had the GG genotype, whereas the second and third sisters, who had type 1 diabetes without AITD, had the AG genotype.
These patients had a stronger association with CTLA4 (odds ratio [OR] = 1.49 for the G allele of the single nucleotide polymorphism rs3087243; 95% CI = 1.29-1.72) than did the TPOAbs-negative patients (p = 0.0004; OR = 1.16; 95% CI = 1.10-1.24) or type 1 diabetes patients overall (OR = 1.20; 95% CI = 1.13-1.27).
In the case-only statistical interaction analysis between rs3772534 and rs3087243, there was also no support for an effect (1994 T1D affected offspring, and 3215 cases, P=0.92).
The results of our study suggest no significant association between CD28 rs1980422, CCL5 rs2107538, CTLA-4 exon 1 +49A>G rs231775 and rs3087243 gene polymorphisms and RA in the Polish population.
In conclusion, our results suggest that the -319C/+49G/CT60G haplotype of CTLA-4 gene is a genetic marker of susceptibility to RA in Western Mexico, whereas the rs3087243 SNP confers protection against this disease.