Recently, different microRNA (miRNA) gene polymorphisms have been evaluated in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Graves’ disease (GD). In the present study, we examined three single-nucleotide polymorphisms (SNPs) located in the pre-miR-146a (rs2910164G/C), pre-miR-196a-2 (rs11614913C/T), and pre-miR-499 (rs3746444A/G) genes. Our study population included 900 Mexican patients with RA, SLE, or GD, as well as 486 healthy control individuals with no family history of inflammatory or autoimmune diseases. Genotyping was performed using TaqMan probes and a 5′ exonuclease assay. None of the investigated SNPs were associated with RA or GD susceptibility under any genetic model (co-dominant, recessive, or dominant). Genotype and allele frequencies of the miR-196a-2 rs11614913C/T polymorphism were similar between SLE cases and controls. In contrast, the miR-146a rs2910164G/C and miR-499 rs3746444A/G polymorphisms were associated with SLE susceptibility. These SNPs were not associated with lupus nephritis (LN). Our results suggest that polymorphisms in miR-146a, miR-196a-2, and miR-499 are not associated with RA or GD susceptibility. This is the first report documenting that the miR-146a rs2910164G/C and miR-499 rs3746444 polymorphisms are associated with SLE susceptibility but not with LN.

Our data provide the first demonstration that PTPN22 R620W confers GD susceptibility among Latin-American patients. Moreover, this is the second report documenting the association of PTPN22 R263Q with protection against SLE and RA.

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IntroductionITGAM has consistently been associated with susceptibility to systemic lupus erythematosus (SLE) in many ethnically diverse populations. However, in populations with higher Amerindian ancestry (like Yucatan) or highly admixed population (like Mexican), ITGAM has seldom been evaluated (except few studies where patients with childhood-onset SLE were included). In addition, ITGAM has seldom been evaluated in patients with rheumatoid arthritis (RA). Here, we evaluated whether four single nucleotide polymorphisms (SNPs), located within ITGAM, were associated with SLE and RA susceptibility in patients from Mexico.MethodsOur study consisted of 1,462 individuals, which included 363 patients with SLE (292 from Central Mexico and 71 from Yucatan), and 621 healthy controls (504 from Central Mexico and 117 from Yucatan). Our study also included 478 patients with RA from Central Mexico. TaqMan assays were used to obtain the genotypes of the four SNPs: rs34572943 (G/A), rs1143679 (G/A), rs9888739 (C/T), and rs1143683 (C/T). We also verified the genotypes by Sanger sequencing. Fisher's exact test and permutation test were employed to evaluate the distribution of genotype, allele, and haplotype between patients and controls.ResultsOur data show that all four ITGAM SNPs are significantly associated with susceptibility to SLE using both genotypic and allelic association tests (corrected for multiple testing, but not for population stratification). A second study carried out in patients from Yucatan, a southeastern part of Mexico (with a high Amerindian ancestry), also replicated SLE association with all four SNPs, including the functional SNP, rs1143679 (OR = 24.6 and p = 9.3X10-6). On the other hand, none of the four SNPs are significant in RA after multiple testing. Interestingly, the GACC haplotype, which carries the ITGAM rs1143679 (A) minor allele, showed an association with protection against RA (OR = 0.14 and p = 3.0x10-4).ConclusionOur data displayed that ITGAM is a risk factor to SLE in individuals of Mexican population. Concurrently, a risk haplotype in ITGAM confers protection against RA.

The present study is the first to document an association between VEGFA -1154G/A and reduced risk in women with RA but not with SLE.