Interactions between TNFAIP3, PTPN22, and TRAF1-C5 gene polymorphisms in patients with primary Sjögren's syndrome.

Objectives: The aim of our study was to investigate whether TNFAIP3, PTPN22, and TRAF1-5 single nucleotide polymorphisms (SNPs) are associated with susceptibility, severity, or serological markers in primary Sjögren's syndrome (pSS). Patients and methods: The cases and controls study was conducted between December 2021 and June 2022. TNFAIP3 rs10499194C/T, rs6920220G/A, and rs2230926T/G, PTPN22 rs2476601C/T and rs33996649G/A, and TRAF1-C5 rs10818488G/A polymorphisms were genotyped in 154 female pSS patients (mean age: 45.2±6.8 years) and 313 female control subjects (mean age: 50.3±7.5 years) using the TaqMan® SNP genotyping assay. An association analysis between TNFAIP3, PTPN22, and TRAF1-C5 SNPs and susceptibility, clinical characteristics, and serological markers of pSS was performed. Interactions between TNFAIP3, PTPN22, and TRAF1-C5 SNPs were also evaluated in patients and controls. Results: The genotype and allele frequencies showed no association with susceptibility, severity, or serological markers of pSS. Nevertheless, several interactions between TNFAIP3 and TRAF1-C5 or TNFAIP3, PTPN22, and TRAF1-C5 genotypes were associated with susceptibility to pSS (p<0.01). Conclusion: Individual TNFAIP3, PTPN22, and TRAF1-C5 SNPs are not associated with susceptibility, severity, or serological markers of pSS. However, genetic interactions between TRAF1-C5 and TNFAIP3 or TNFAIP3, PTPN22, and TRAF1-C5 SNPs are risk factors for pSS.

ELANE rs17223045C/T and rs3761007G/A variants: Protective factors against COVID-19.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for causing coronavirus disease 2019 (COVID-19). The development and severity of this infectious disease is influenced by a combination of environmental and genetic factors. Angiotensin-converting enzyme 2 (ACE2) facilitates SARS-CoV-2 entry into human cells, with transmembrane serine protease 2 (TMPRSS2) playing a crucial role in S protein priming. Other proteases, such as cathepsin L and elastase, neutrophil-expressed (ELANE), have the capability to prime the S protein and contribute to SARS-CoV-2 infection. ELANE variants have not been previously examined in COVID-19 patients. We aimed to assess the association of single nucleotide variants (SNVs) within ELANE with COVID-19 and biochemical markers. The study included 319 SARS-CoV-2-infected patients and 288 controls. Genotyping of ELANE rs17216663C/T (Pro257Leu), rs17223045C/T (As1n30Asn), and rs3761007G/A was conducted using a 5'-nuclease allelic discrimination assay (TaqMan assay). Our findings indicate that ELANE rs17223045C/T (C vs T: odds ratio [OR] 0.08, P = 0.005, and CC vs CT: OR 0.08, P = 0.005) and rs3761007G/A (G vs A: OR 0.38, P = 0.009, and GG vs GA: OR 0.40, P = 0.008) confer protection against COVID-19. However, these variants were not associated with biochemical markers. In conclusion, our data suggests that ELANE rs17223045C/T and rs3761007G/A SNVs may play a protective role against COVID-19.

The functional TNFAIP3 rs2230926T/G (Phe127Cys) variant confers risk to systemic lupus erythematosus in a Latin American population.

TNFAIP3 is a classical systemic lupus erythematosus (SLE)-associated risk locus identified by genome-wide association studies (GWASs) and replicated by candidate gene association studies primarily in Caucasians and Asians. However, in Latin American populations, its role on SLE susceptibility is not known. We conducted a case-control study to evaluate whether the TNFAIP3 rs2230926T/G (Phe127Cys) variant is associated with risk of developing SLE in a cohort of Mexican patients. The TNFAIP3 rs2230926T/G variant was analyzed in 561 patients with SLE and 499 control subjects, using TaqMan probes. We found that the G allele was associated with susceptibility to SLE under the allelic (OR 2.09, p = 0.005) and genotypic (OR 2.14, p = 0.004) models. In conclusion, our results show that TNFAIP3 rs2230926T/G is a risk factor for the development of SLE in the Mexican population.

CD147 rs8259T>A Variant Confers Susceptibility to COVID-19 Infection within the Mexican Population.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Clinical manifestations of COVID-19 range from mild flu-like symptoms to severe respiratory failure. Nowadays, extracellular matrix metalloproteinase inducer (EMMPRIN), also known as cluster of differentiation 147 (CD147) or BASIGIN, has been studied as enabling viral entry and replication within host cells. However, the impact of the CD147 rs8259T>A single nucleotide variant (SNV) on SARS-CoV-2 susceptibility remains poorly investigated. OBJECTIVE: To investigate the impact of rs8259T>A on the CD147 gene in individuals from Mexico with COVID-19 disease. METHODS: We genotyped the CD147 rs8359T>A SNV in 195 patients with COVID-19 and 185 healthy controls from Mexico. In addition, we also measured the expression levels of CD147 and TNF mRNA and miR-492 from whole blood of patients with COVID-19 through RT-q-PCR. RESULTS: We observed a significant association between the CD147 rs8259T>A SNV and susceptibility to COVID-19: T vs. A; OR 1.36, 95% CI 1.02-1.81; p = 0.037; and TT vs. AA; OR 1.77, 95% CI 1.01-3.09; p = 0.046. On the other hand, we did not find differences in CD147, TNF or miR-492 expression levels when considering the genotypes of the CD147 rs8259T>A SNV. CONCLUSIONS: Our results suggest that the CD147 rs8259T>A variant is a risk factor for COVID-19.

No association of eight TNFAIP3 single nucleotide variants to rheumatoid arthritis in Mexicans.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of autoimmune origin with many associated genetic traits, including genes related to the control of inflammation. The A20 protein, encoded by the TNFAIP3 gene, is a negative regulator of NF-kB mediated inflammation. Several single nucleotide variants (SNVs) of TNFAIP3 are associated with susceptibility to RA in different ethnic groups, none of which has been evaluated in Mexican patients. OBJECTIVE: To examine the possible association of eight TNFAIP3 SNVs in Mexican patients with RA. MATERIALS: We studied 471 patients with RA and 500 controls, as well as eight TNFAIP3 SNVs: including, rs10499194C/T, rs6920220G/A, and rs2230926T/G, which have been associated with RA in European or Asian patients, in addition to rs373421182G/C, rs139054966T/G, rs5029924C/T, rs59693083A/G and rs61593413T/A, not previously examined in RA. All SNVs were evaluated by means of an allelic discrimination assay using TaqMan probes. RESULTS: The allelic and genotypic frequencies of all SNVs examined were similar between cases and controls, and none of them was associated with RA under the allelic, codominant, dominant, and recessive models, as well as in haplotype combinations. CONCLUSION: Our data indicate that TNFAIP3 SNVs evaluated herein are not risk factors for RA in Mexican subjects.

TNFSF4 is a risk factor for rheumatoid arthritis but not for primary Sjögren's syndrome in the Mexican population.

PURPOSE: Rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS) are autoimmune diseases (ADs) characterized by joint damage and involvement of the salivary glands, respectively. ADs share some susceptibility loci, such as TNFSF4, which is a classical susceptibility gene associated with systemic lupus erythematosus, but its role in RA and pSS is not yet clear. Thus, the aim of this study was to determine whether three TNFSFS4 polymorphisms are associated with RA and pSS. METHODS: Our case-control study included 500 controls, 459 patients with RA, and 210 patients with pSS from Mexico. TNFSF4 single nucleotide polymorphisms (SNPs) rs1234315C/T, rs2205960G/T, and rs704840T/G were genotyped using TaqMan probes and discrimination allelic assay. RESULTS: The three TNFSF4 SNPs were associated with susceptibility to RA (rs1234315C/T: odds ratio [OR] 1.4, p = 0.01; rs2205960G/T: OR 1.23, p = 0.03; rs704840T/G: OR 1.24, p = 0.02). An association between TNFSF4 rs1234315C/T and pSS was also observed (OR 1.28, p = 0.04), however, after Bonferroni correction, this association was lost. CONCLUSION: Our data suggest that TNFSF4 could be a risk factor in RA but not pSS in a Mexican population.

A Novel Technique for the Evaluation and Interpretation of Elastography in Salivary Gland Involvement in Primary Sjögren Syndrome.

Ultrasound (US) of major salivary glands (MSG) evaluates echogenicity, border features and vascularization, with elastography, it can detect tissue elasticity and glandular fibrosis, related to inflammation in Primary Sjögren's syndrome (pSS). This study aimed to develop a novel technique by pixel analysis for evaluation and interpretation of elastography in MSG in pSS. A cross-sectional and observational multicenter study was conducted. The US of MSG performed in orthogonal planes in grayscale, Doppler, and shear-wave elastography. For elastography images of each gland were analyzed with the open-source program ImageJ to perform a pixel analysis. Statistical analysis was performed with the IBM-SPSS v25 program. Fifty-nine women with a mean age of 57.69 (23-83) years were recruited; pSS mean duration of 87 (5-275) months, and 12 healthy women without sicca symptoms as a control group with a mean age of 50.67 (42-60) years. Intragroup analysis showed p-values >0.05 between sicca symptoms, ocular/dryness tests, biopsy, US, and pixel analysis; correlation between Hocevar and pixel analysis was not found (rho < 0.1, p >0.5). MSG anatomical size was 41.7 ± 28.2 mm vs. 67.6 ± 8.8 mm (p ≤ 0.0001); unstimulated whole saliva flow rate was 0.80 ± 0.80 ml/5 min vs. 1.85 ± 1.27 ml/5 min (p = 0.016). The elastography values (absolute number of pixels) were 572.38 ± 99.21 vs. 539.69 ± 93.12 (p = 0.290). A cut-off point risk for pSS identified with less than 54% of red pixels in the global MSG mass [OR of 3.8 95% CI (1.01-15.00)]. Pixel analysis is a new tool that could lead to a better understanding of the MSG chronic inflammatory process in pSS.

The rs8176740 T/A and rs512770 T/C Genetic Variants of the ABO Gene Increased the Risk of COVID-19, as well as the Plasma Concentration Platelets.

We conducted a case-control study in order to evaluate whether ABO gene polymorphisms were associated with a high risk of developing COVID-19 in a cohort of patients. Six ABO gene polymorphisms (rs651007 T/C, rs579459 T/C, rs495828 T/G, rs8176746 A/C, rs8176740 T/A, and rs512770 T/C) were determined using TaqMan genotyping assays in a group of 415 COVID-19 patients and 288 healthy controls. The distribution of rs651007 T/C, rs579459 T/C, rs495828 T/G, and rs8176746 A/C polymorphisms was similar in patients and healthy controls. Nonetheless, under co-dominant (OR = 1.89, pCCo-dominant = 6 × 10-6), recessive (OR = 1.98, pCRecessive = 1 × 10-4), and additive (OR = 1.36, pCAdditive = 3 × 10-3) models, the TT genotype of the rs8176740 T/A polymorphism increased the risk of developing COVID-19. In the same way, under co-dominant, recessive, and additive models, the TT genotype of the rs512770 T/C polymorphism was associated with a high risk of developing COVID-19 (OR = 1.87, pCCo-dominant = 2 × 10-3; OR = 1.87, pCRecessive = 5 × 10-4; and OR = 1.35, pCAdditive = 4 × 10-3, respectively). On the other hand, the GTC and GAT haplotypes were associated with a high risk of COVID-19 (OR = 5.45, pC = 1 × 10-6 and OR = 6.33, pC = 1 × 10-6, respectively). In addition, the rs8176740 TT genotype was associated with high-platelet plasma concentrations in patients with COVID-19. Our data suggested that the ABO rs512770 T/C and rs8176740 T/A polymorphisms increased the risk of developing COVID-19 and the plasma concentration of platelets.

TLR4 and TLR9 polymorphisms are not associated with either rheumatoid arthritis or systemic lupus erythematosus in Mexican patients.

Toll-like receptor (TLR)-mediated signaling pathways induce a proinflammatory microenvironment to eradicate pathogens. However, in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), TLRs can promote chronic inflammation. It has been shown that some TLR4 and TLR9 single nucleotide polymorphisms (SNPs) are risk factors for RA and SLE, but these findings have not been replicated in all populations; thus, results are inconclusive. We evaluated the TLR4 Asp299Gly, Thr399Ile, - 1892G/A SNPs, and the TLR9 Pro545Pro SNP to assess potential associations with RA and SLE in Mexican patients. This study included 474 patients with RA, 283 patients with SLE, and 424 healthy controls. We used a 5' nuclease allelic discrimination assay to genotype individuals for the four TLR4 and TLR9 polymorphisms. We found that the genotype or allelic frequencies of the TLR4 Asp299Gly, Thr399Ile, - 1892G/A, and TLR9 Pro545Pro polymorphisms were similar between patients and controls. We found no association under different genetic models. A haplotype analysis of TLR4 showed no association with either RA or SLE. We found no significant differences in the allelic or genotypic frequencies of TLR4 Asp299Gly, Thr399IIe, - 1892G/A, or TLR9 Pro545Pro between patients and controls. These findings suggested that these variants are not risk factors for RA or SLE in Mexican patients.

BLK and BANK1 variants and interactions are associated with susceptibility for primary Sjögren's syndrome and with some clinical features.

BLK and BANK1 in primary Sjögren's syndrome (pSS) have scarcely been evaluated and the results are inconclusive. The aim of our study was to determine whether single nucleotide variants (SNVs) located within BLK or BANK1 are associated with susceptibility, clinical and serological features, and smoking in pSS. BLK rs13277113A/G, BANK1 rs10516487G/A and rs3733197G/A were genotyped in 203 cases and 424 controls using a TaqMan® SNP genotyping assay. The BLK rs13277113A allele showed association with pSS under the allelic (OR 1.35, p = 0.02), and recessive (OR 1.83, p = 0.003) model, while, BANK1 rs3733197G/A showed association under the dominant model (OR 2.90, p = 0.043). Interactions between BANK1 and BLK genotypes also showed association (OR 2.36, p < 0.0001). In addition, BLK rs13277113A/G was associated with protection against arthritis and BANK1 rs10516487G/A with both arthritis and keratoconjunctivitis sicca, meanwhile, BANK1 rs3733197G/A was associated with smoking in patients with pSS. This is the first study to describe an association between BLK and susceptibility to pSS in a Latin-American population. Our data also shows a first evidence of association between interactions of BLK and BANK1 in pSS, and association of BLK and BANK1with arthritis, keratoconjunctivitis sicca and smoking in patients with pSS.

TNFSF4 is a risk factor to systemic lupus erythematosus in a Latin American population.

OBJECTIVE: The aim of this study was to examine the association of three TNFSF4 single nucleotide variants (SNVs) with systemic lupus erythematosus (SLE) susceptibility in Mexican patients. METHODS: Genotypes of the TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G SNVs were determined using a TaqMan assay. In our study, we included 395 patients with SLE and 500 controls. RESULTS: Our information shows a significant difference in the allelic and genotypic frequency of the three TNFSF4 SNVs between cases and controls. Thus, our data showed an association between TNFSF4 rs1234315T/C (T vs. C, OR 1.40, p = 0.00087), rs2205960G/T (G vs. T, OR 1.32, p = 0.0037), and rs704840T/G (T vs. G, OR 1.41, p = 0.0003) and SLE susceptibility in Mexican subjects. Besides, we conducted a meta-analysis to determine the role of TNFSF4 rs2205960G/T and SLE susceptibility; our results showed that this variant is a risk factor for SLE in Latin Americans and Asians. CONCLUSION: Our results show that TNFSF4 rs1234315T/C, rs2205960G/T, and rs704840T/G are risk factors to SLE in Mexicans. This is the first study to document an association between TNFSF4 rs704840T/G and SLE in a Latin American population. In addition, our meta-analysis showed that TNFSF4 rs2205960G/T is a risk factor for Asians and Latin Americans. Key Point • The TNFSF4 rs1234315T/C, rs2205960G/T, and rs704849T/G SNVs are risk factors to SLE in patients from Mexico.

Correction to: Serum substance P: an indicator of disease activity and subclinical inflammation in rheumatoid arthritis.

Following publication, it was brought to the authors' attention by Dr. Julia Toscano-Garibay that she did not participate as a reviewer of the final version of this manuscript prior to its submission and publication in Clinical Rheumatology.

Association of BLK and BANK1 Polymorphisms and Interactions With Rheumatoid Arthritis in a Latin-American Population.

INTRODUCTION: BLK has been identified as a risk factor to rheumatoid arthritis (RA) primarily in Asian or European-derived populations. However, this finding has not been evaluated in other populations such as Latin-Americans, except for Colombians. On the other hand, BANK1 single nucleotide variants (SNVs) have been scarcely studied in RA patients. OBJECTIVE: The aim of this study was to determine whether the BLK rs2736340T/C, rs13277113A/G, and BANK1 rs10516487G/A (R61H) and rs3733197G/A (A383T) polymorphisms are risk factors to RA in a sample of patients from Central Mexico. MATERIALS AND METHODS: We studied 957 women; 487 controls and 470 patients with RA by means of a TaqMan® SNP genotyping assay with fluorescent probes for the BLK rs13277113A/G, rs2736340T/C and BANK1 10516487G/A (R61H) and rs3733197G/A (A383T) variants. RESULT: The BLK rs2736340T/C and rs13277113A/G variants were associated with risk for RA: C vs T; OR 1.39, p = 0.001, and G vs A; OR 1.37, p = 0.004, respectively. In addition, there was also an association between BANK1 R61H and RA: A vs G; OR 1.49, p = 0.003, but no with BANK1 A383T. We also identified an interaction significant between genotypes of BLK rs2736340T/C-BANK1 rs10516487G/A and RA: OR 1.65, p = 0.0001. CONCLUSIONS: Our data suggest that both BLK and BANK1 confer susceptibility to RA in Mexican patients. The individual association of BANK1 rs1054857G/A with RA had not been previously reported in a particular population (except for pooled patients from several countries), therefore, our study presents the first evidence of association between this BANK1 variant and RA.

ITGAM is a risk factor to systemic lupus erythematosus and possibly a protection factor to rheumatoid arthritis in patients from Mexico.

INTRODUCTION: ITGAM 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. METHODS: Our 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. RESULTS: Our 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). CONCLUSION: Our 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 AIRE Ser196Ser synonymous variant is a risk factor for systemic lupus erythematosus.

The AIRE gene influences the expression of a wide array of self-antigens in the thymus, and is essential to the negative selection of self-reactive T cells and establishment of central tolerance. Single nucleotide variants (SNVs) such as rs878081C/T (Ser196Ser) and rs2075876G/T at this locus have been associated with susceptibility to rheumatoid arthritis, mainly in Asian populations, but its role in systemic lupus erythematosus (SLE) has not been documented. We performed a case-control association study with 379 SLE patients and 460 controls from central Mexico. In addition, we replicated our finding in another group of 179 SLE patients and 97 controls from the same region of Mexico. In the first group, we identified that the AIRE Ser196Ser synonymous variant was associated with SLE (OR 1.4, p = 0.009), meanwhile, in the second group we observed the following: OR 1.7, p = 0.024. No association was found between these AIRE SNVs and lupus nephritis. Our results suggest that AIRE is a risk factor for SLE in our population. This study is the first to document an association between AIRE and SLE susceptibility.

Catalytically Impaired TYK2 Variants are Protective Against Childhood- and Adult-Onset Systemic Lupus Erythematosus in Mexicans.

Type I interferon (IFN-I) pathway plays a central role in the systemic lupus erythematosus (SLE) pathogenesis. Recent data suggest that SLE is associated with variants in IFN-I genes, such as tyrosine kinase 2 (TYK2), which is crucial in anti-viral immunity. Here, five TYK2 single nucleotide polymorphisms (SNPs) were genotyped in 368 childhood-onset SLE Mexican patients and 516 sex-matched healthy controls. Allele frequencies were also estimated in four indigenous groups. SLE protection was associated with TYK2 risk infection variants affecting residually its catalytic domain, rs12720356 (OR = 0.308; p = 0.041) and rs34536443 (OR = 0.370; p = 0.034), but not with rs2304256, rs12720270, and rs280500. This association was replicated in a 506 adult-onset SLE patients sample (OR = 0.250; p = 0.005, and OR = 0.277; p = 0.008, respectively). The minor alleles of both associated SNPs had a lower frequency in Mestizos than in Spaniards and were absent or rare in indigenous, suggesting that the presence of these alleles in the Mexican Mestizo population was derived from the Spaniards. For the first time, we report genetic variants with a protective effect in childhood- and adult-onset SLE Mexican population. Our results suggest that the frequency of IFN-I alleles associated with SLE, may have been shaped in populations exposed to infectious diseases for long periods, and this could be an explanation why Native American ancestry is associated with a higher SLE prevalence and an earlier onset.

BLK and BANK1 polymorphisms and interactions are associated in Mexican patients with systemic lupus erythematosus.

OBJECTIVES: The BLK and BANK1 genes have been consistently associated with systemic lupus erythematosus (SLE), primarily in European or Asian-derived populations. However, this finding has not been replicated in Latin-American patients. METHODS: Our study included 881 women from Mexico: 487 healthy controls and 394 SLE patients. The BLK rs13277113A/G-rs2736340T/C as well as BANK1 rs10516487G/A (R61H)-rs3733197G/A (A383T) single nucleotide polymorphisms (SNPs) were evaluated using a TaqMan® SNP genotyping assay. RESULTS: Our data showed that the BLK rs2736340T/C and rs13277113A/G polymorphisms are associated with susceptibility to SLE (C vs T, OR 1.60, p = 2×10-5; G vs A, OR 1.53, p = 9 × 10-5, respectively). We also identified an association between the functional BANK1 R61H polymorphism and SLE (A vs G, OR 1.56, p = 0.002). In addition, we observed a genetic interaction between BLK (rs2736340T/C, rs13277113A/G) and BANK1 (R61H and A383T) associated with susceptibility to SLE. CONCLUSION: This is the first study documenting an association between BLK and BANK1 and SLE in a Latin-American population. Our data confirm previous reports: BLK and BANK1 are factors associated with SLE. Thus, both genes are universal loci for this autoimmune disease.

The VEGFA -1154G/A polymorphism is associated with reduced risk of rheumatoid arthritis but not with systemic lupus erythematosus in Mexican women.

BACKGROUND: Levels of circulating vascular endothelial growth factor (VEGF) (a potent endothelial-cell-specific angiogenic factor) have been correlated with disease activity in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). In addition, several single nucleotide polymorphisms (SNPs), including the VEGFA -2578C/A, have been associated with RA in some populations. By contrast, the role of different VEGFA SNPs in the susceptibility to SLE has received little attention. Thus, the present study aimed to determine whether the VEGFA -2578C/A, -1154G/A and -634G/C polymorphisms confer risk or were associated with reduced risk of RA or SLE in a Mexican population. METHODS: The present study included 903 women from Mexico: 405 were patients with RA, 282 had SLE and 216 were healthy individuals. The genotypes were obtained with TaqMan probes. RESULTS: The data obtained in the present study suggest that the VEGFA -2578C/A and -634G/C polymorphisms are not risk factors for RA or SLE; however, VEGFA -1154G/A was associated with reduced risk in women with RA (odds ratio = 0.6, pc  = 0.0051) but not with SLE (odds ratio = 0.7, pc  = 0.13). CONCLUSIONS: 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.

Tumor necrosis factor gene polymorphisms are associated with systemic lupus erythematosus susceptibility or lupus nephritis in Mexican patients.

The TNF -238G/A (rs361525) and -308G/A (rs1800629) polymorphisms have consistently been associated with systemic lupus erythematosus (SLE) in several populations; however, these findings have not been verified in all populations. Here, we aimed to examine whether the TNF -238G/A, -308G/A, -376G/A (rs1800750), and -1031T/C (rs1799964) polymorphisms confer SLE or lupus nephritis (LN) susceptibility in a Mexican population. Our study included 442 patients with SLE and 495 controls. For genotyping, we used the TaqMan 5' allele discrimination assay. The TNF -238G/A and -1031T/C polymorphisms were associated with SLE susceptibility (odds ratio (OR) 2.1, p = 0.0005 and OR 1.4, p = 0.003, respectively). Gender stratification showed a strong association between TNF -238G/A and SLE in women (OR 2.2, p = 0.00006), while TNF -1031T/C had an OR of 1.5 (p = 0.007). With regard to the TNF -376G/A polymorphism, this also showed association with SLE susceptibility (OR 1.95, p = 0.036) and LN (OR 3.5, p = 0.01). In conclusion, our study provides the first demonstration of association between the TNF -376G/A polymorphism and SLE and LN susceptibility. In addition, our study is the second documenting an association of TNF -1031T/C with SLE susceptibility. We also observed a strong association between TNF -238G/A and SLE susceptibility. The TNF 308G/A polymorphism was not associated with SLE or LN.

Tumor necrosis factor (TNF) and TNFR1 polymorphisms are not risk factors for rheumatoid arthritis in a Mexican population.

Tumor necrosis factor (TNF) plays an important role in the pathogenesis of rheumatoid arthritis (RA). Different genetic variants including the TNF -308G/A polymorphism are associated with RA susceptibility. However, these findings have not been replicated in all populations. The aim of this study was to determine whether the TNF -1031T/C (rs1799964), -376G/A (rs1800750), -308G/A (rs1800629) -238G/A (rs361525), and TNFR1 -609G/T polymorphisms are associated with RA susceptibility in a sample of Mexican patients. Our study included 499 patients with RA and 492 healthy controls. The genotypes of the TNF polymorphisms were obtained using TaqMan assay. The genotype and allele frequencies of the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms were similar among RA cases versus healthy controls, and no association with RA susceptibility was identified. Our results suggest that the TNF -1031T/C, -376G/A, -308G/A, -238G/A, and TNFR1 -609G/T polymorphisms are not associated with RA susceptibility in a sample of Mexican patients.