Decreased Systemic Lupus Erythematosus Risk Research Articles

TP53 Gene Polymorphism (Rs1042522) in Rheumatoid Arthritis and Systemic Lupus Erythematosus: An Updated Systematic Review and Meta-Analysis.

The p53 protein has important roles in apoptosis, proliferation, and prevention of DNA damage. Several studies have reported that TP53 gene polymorphism is associated with various autoimmune diseases, including Rheumatoid arthritis (RA) and Systemic lupus erythematosus (SLE). Evaluation of the correlation between TP53 gene rs1042522 polymorphism and RA and SLE risk by meta-analysis. Databases, including PubMed and Scopus, were searched to find studies assessing the association between TP53 gene polymorphism and RA and SLE risk in different populations up to August 2022. The protocol of this article was registered on the International Prospective Register Of Systematic Reviews (PROSPERO number: CRD42022309655). Herein, 7 case-control studies, including 2498 cases and 3799 controls in the SLE group, and 6 case-control studies comprising 1593 cases and 4460 controls in the RA group that investigated rs1042522 SNP were included in the meta-analysis. Herein, CG genotypes were more frequent in healthy participants compared to SLE patients and may associated with a decreased SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.006). Besides, dominant and recessive models of CC+ CG vs. GG were also protective for SLE risk (OR=0.85, CI: 0.76-0.95, P-value <0.004). In summary, this study discloses a weak correlation between rs1042522 and a decreased risk of SLE. However, no significant association was found in RA.

The role of environmental exposures and gene-environment interactions in the etiology of systemic lupus erythematous.

Systemic lupus erythematosus (SLE) is a complex, chronic autoimmune disease, whose etiology includes both genetic and environmental factors. Individual genetic risk factors likely only account for about one-third of observed heritability among individuals with a family history of SLE. A large portion of the remaining risk may be attributable to environmental exposures and gene-environment interactions. This review focuses on SLE risk associated with environmental factors, ranging from chemical and physical environmental exposures to lifestyle behaviors, with the weight of evidence supporting positive associations between SLE and occupational exposure to crystalline silica, current smoking, and exogenous estrogens (e.g., oral contraceptives and postmenopausal hormones). Other risk factors may include lifestyle behaviors (e.g., dietary intake and sleep) and other exposures (e.g., ultraviolet [UV] radiation, air pollution, solvents, pesticides, vaccines and medications, and infections). Alcohol use may be associated with decreased SLE risk. We also describe the more limited body of knowledge on gene-environment interactions and SLE risk, including IL-10, ESR1, IL-33, ITGAM, and NAT2 and observed interactions with smoking, UV exposure, and alcohol. Understanding genetic and environmental risk factors for SLE, and how they may interact, can help to elucidate SLE pathogenesis and its clinical heterogeneity. Ultimately, this knowledge may facilitate the development of preventive interventions that address modifiable risk factors in susceptible individuals and vulnerable populations.

Association of Dietary Quality With Risk of Incident Systemic Lupus Erythematosus in the Nurses' Health Study and Nurses' Health Study II.

Knowledge remains scarce regarding diet and systemic lupus erythematosus (SLE) risk. Our objective was to investigate 4 dietary quality scores and SLE risk overall and by anti-double-stranded DNA (anti-dsDNA) positive versus negative subtypes. We studied 79,568 women in the Nurses' Health Study (1984-2014) and 93,554 in the Nurses' Health Study II (1991-2013). Using validated food frequency questionnaires, we calculated 4 dietary scores: the 2010 Alternative Healthy Eating Index (AHEI-2010), the Alternative Mediterranean Diet Score (aMed), the Dietary Approach to Stop Hypertension (DASH), and the Empirical Dietary Inflammatory Pattern (EDIP). Incident SLE was confirmed by medical record review. Time-varying Cox regression models estimated pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) of SLE risk, overall and by anti-dsDNA, for cumulative average dietary quality score tertiles and individual AHEI-2010 components. We identified 194 incident SLE cases. SLE risk was similar in women with the highest (versus lowest) dietary scores (AHEI-2010 HR 0.78 [95% CI 0.54-1.14], aMed HR 0.82 [95% CI 0.56-1.18], DASH HR 1.16 [95% CI 0.81-1.66], EDIP HR 0.83 [95% CI 0.57-1.21]). No association was demonstrated for anti-dsDNA+ or anti-dsDNA- SLE risk. Women in the highest (versus lowest) AHEI-2010 tertile of nut/legume intake had a decreased SLE risk (HR 0.59 [95% CI 0.40-0.87]). No association was demonstrated for other AHEI-2010 components and SLE risk. We observed no association between long-term adherence to the AHEI-2010, aMed, DASH, or EDIP scores with SLE risk, suggesting a large effect of dietary quality on SLE risk is unlikely. However, potential reduction in overall SLE risk with high nut/legume intake warrants further investigation.

Association of LncRNA-GAS5 gene polymorphisms and PBMC LncRNA-GAS5 level with risk of systemic lupus erythematosus in Chinese population.

Growth arrest‐specific 5 (GAS5) is a kind of long non‐coding RNAs (lncRNAs). Previous studies showed that down‐regulation of LncRNA‐GAS5 was involved in the development of systemic lupus erythematosus (SLE). However, the regulatory mechanism of down‐expressed LncRNA‐GAS5 in SLE remains obscure. In this study, we aimed to investigate the association of LncRNA‐GAS5 polymorphism with SLE risk. And further explore how LncRNA‐GAS5 is involved in the occurrence of SLE. Here, we evaluated the relationship between the risk for the development of SLE and the 5‐base pair (AGGCA/‐) insertion/deletion (I/D) polymorphism (rs145204276) in the LncRNA‐GAS5 promoter region. A custom 36‐Plex SNPscan kit was used for genotyping the LncRNA‐GAS5 polymorphisms. The LncRNA‐GAS5 and miR‐21 target prediction was performed using bioinformatics software. Enzyme‐linked immunosorbent assay (ELISA) and quantitative real‐time PCR (qRT‐PCR) were performed to assess GAS5 and miR‐21 mRNA expression and PTEN protein expression. The results revealed that rs145204276 resulted in a decreased risk of SLE (DD genotypes vs II genotypes: adjusted OR = 0.538, 95% CI, 0.30‐0.97, P = .039; ID genotypes vs II genotypes: adjusted OR = 0.641, 95% CI, 0.46‐0.89, P = .007; ID/DD genotypes vs II genotypes: adjusted OR = 0.621, 95% CI, 0.46‐0.84, P = .002; D alleles vs I alleles: adjusted OR = 0.680, 95% CI, 0.53‐0.87, P = .002). A reduced incidence of renal disorders in SLE was found to be related to ID/DD genotypes and D alleles (ID/DD genotypes vs II genotypes: OR = 0.57, 95% CI, 0.36‐0.92, P = .020; D alleles vs I alleles: OR = 0.63, 95% CI, 0.43‐0.93, P = .019). However, no significant association of rs2235095, rs6790, rs2067079 and rs1951625 polymorphisms with SLE risk was observed (P > .05). Additionally, haplotype analysis showed that a decreased SLE risk resulted from the A‐A‐C‐G‐D haplotype (OR = 0.67, 95% CI, 0.49‐0.91, P = .010). Also, patients in the SLE group showed a down‐regulated expression of LncRNA‐GAS5 and PTEN than the healthy volunteers; however, patients with rs145204276 ID/DD genotypes showed up‐regulated expression of LncRNA‐GAS5 and PTEN compared with patients carrying the II genotype. Furthermore, the miR‐21 levels were considerably up‐regulated in the SLE group than the healthy volunteers, and patients with rs145204276 ID/DD genotype had lower miR‐21 levels than the ones with the II genotype. Thus, we found that the LncRNA‐GAS5/miR‐21/PTEN signalling pathway was involved in the development of SLE, where LncRNA‐GAS5 acted as an miR‐21 target, and miR‐21 regulated the expression of PTEN. These findings indicated that the rs145204276 ID/DD genotypes in the LncRNA‐GAS5 gene promoter region may be protected against SLE by up‐regulating the expression of LncRNA‐GAS5, which consecutively regulated miR‐21 and PTEN levels.

Relationship of Cigarette Smoking and Alcohol Consumption to Incidence of Systemic Lupus Erythematosus in a Prospective Cohort Study of Black Women.

Systemic lupus erythematosus (SLE) affects black women more frequently than other racial/gender groups. In past studies, largely consisting of white and Asian cohorts, cigarette smoking was associated with increased SLE risk, and moderate alcohol consumption was associated with decreased SLE risk. The aim of this study was to assess associations of smoking and alcohol consumption with the risk of incident SLE among black women, using data from a long-term, prospective, follow-up study. The Black Women's Health Study enrolled 59,000 black women in 1995 and collected data on demographics, health status, and medical and lifestyle variables. Follow-up questionnaires that were given every 2 years identified incident disease and updated risk factors. Cases of incident SLE that met the American College of Rheumatology revised criteria for SLE as updated in 1997 were confirmed through medical record review. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CI) for associations of cigarette smoking and alcohol intake with incidence of SLE. A total of 127 incident SLE cases from 1995 to 2015 (mean age 43 years at diagnosis) were confirmed. Compared to never smokers, the risk of SLE among ever smokers was elevated, but not significantly (HR 1.45 [95% CI 0.97-2.18]). Risk was similar for current and past smoking and increased nonsignificantly with increasing pack-years. The HR was 0.71 (95% CI 0.45-1.12) for current drinking relative to never drinking, with a HR of 0.43 (95% CI 0.19-0.96) for ≥4 drinks/week. Findings from this large study of SLE risk among black women are consistent with previous results from studies in other populations of increased risk of SLE associated with cigarette smoking and decreased risk with moderate alcohol consumption.

Associations of HSP90AA2 gene polymorphisms with disease susceptibility, glucocorticoids efficacy and health-related quality of life in Chinese systemic lupus erythematosus patients.

Although the current glucocorticoids (GCs) treatment for systemic lupus erythematosus (SLE) is effective to a certain extent, the difference in therapeutic effect between patients is still a widespread problem. Some patients can have repeated attacks that greatly diminish their quality of life. This study was conductedto investigate the relationship between HSP90AA2 polymorphisms and disease susceptibility, GCs efficacy and health-related quality of life (HRQoL) in Chinese SLE patients.A case-control study was performed in 470 SLE patients and 470 normal controls. Then, 444 patients in the case group were followed up for 12weeks to observe efficacy of GCs and improvement of HRQoL. Two single nucleotide polymorphisms (SNPs) of HSP90AA2 were selected for genotyping: rs1826330 and rs6484340. HRQoL was assessed using the SF-36 questionnaire. The minor T allele of rs1826330 and the TT haplotype formed by rs1826330 and rs6484340 showed associations with decreased SLE risk (T allele: PBH = 0.022; TT haplotype: PBH = 0.033). A significant association between rs6484340 and improvement of HRQoL was revealed in the follow-up study. Five subscales of SF-36 were appeared to be influenced by rs6484340: total score of SF-36 (additive model: PBH = 0.026), physical function (additive model: PBH = 0.026), role-physical (recessive model: PBH = 0.041), mental health (dominant model: PBH = 0.047), and physical component summary (additive model: PBH = 0.026). No statistical significance was found between HSP90AA2 gene polymorphisms and GCs efficacy. These results revealed a genetic association between HSP90AA2 and SLE. Remarkably, HSP90AA2 has an impact on the improvement of HRQoL in Chinese population with SLE.

Meta-analysis of programmed cell death 1 polymorphisms with systemic lupus erythematosus risk.

The association of polymorphisms in programmed cell death 1 (PDCD1) gene with systemic lupus erythematosus (SLE) risk is inconsistent across different studies. This meta-analysis is aimed to provide reliable evidence to the association of five common PDCD1 polymorphisms (PD1.1, PD1.2, PD1.3, PD1.5 and PD1.6) with SLE risk. A total of 28 studies with 4,344 SLE cases and 5,474 healthy controls were included in this meta-analysis. PD1.3 polymorphism was significantly associated with SLE in the overall population (A vs. G: OR = 1.35, 95% CI = 1.12-1.63; GA vs.GG: OR = 1.41, 95% CI = 1.12-1.76; AA+GA vs. GG: OR = 1.41, 95% CI = 1.13-1.7). In the stratified analyses based on ethnicity, we found a significant association in Caucasians and in Mexicans. In the subgroup analyses by gender, a significant association was found between PD1.3 polymorphism and SLE risk in males. The results also suggested an association between the PD1.6 polymorphism and decreased SLE risk (A vs. G: OR = 0.84, 95% CI = 0.73-0.96). Our meta-analysis revealed that PD1.3 polymorphism may increase the susceptibility to SLE, particularly in Caucasians, while PD1.6 may be a protective factor to SLE.

Influence of Alcohol Consumption on the Risk of Systemic Lupus Erythematosus Among Women in the Nurses' Health Study Cohorts.

Moderate alcohol consumption has antiinflammatory properties and is associated with reduced cardiovascular disease and rheumatoid arthritis risks. We investigated the association between alcohol consumption and systemic lupus erythematosus (SLE) risk among women followed in the Nurses' Health Study (NHS) cohorts. We conducted a prospective cohort analysis among 204,055 women in NHS (1980-2012) and NHSII (1989-2011) who were free of connective tissue disease and provided alcohol information at baseline. Alcohol consumption was assessed using a semiquantitative food frequency questionnaire every 2-4 years. We validated incident SLE through medical record review after self-report. Cox proportional hazards models estimated hazard ratios (HRs) for SLE based on cumulative average alcohol intake, adjusting for potential confounders. Results were meta-analyzed using DerSimonian and Laird random-effects models. We further investigated SLE risk associated with wine, beer, and liquor intake. We identified 125 incident SLE cases in NHS and 119 in NHSII. Mean ± SD age at SLE diagnosis was 55.8 ± 9.5 years in NHS and 43.4 ± 7.7 years in NHSII. Compared to no alcohol intake, the meta-analyzed multivariable HR for cumulative alcohol consumption ≥5 gm/day was 0.61 (95% confidence interval [95% CI] 0.41-0.89). When limiting alcohol exposure to >4 years prior to SLE diagnosis, the multivariable HR was similar: 0.61 (95% CI 0.41-0.91). Women who drank ≥2 servings/week of wine had significantly decreased SLE risk (HR 0.65, 95% CI 0.45-0.96) compared to women who did not drink wine. In these large prospective cohorts, we demonstrated an inverse association between moderate alcohol consumption (≥5 grams or 0.5 drink/day) and SLE risk in women.

Environmental exposures and the development of systemic lupus erythematosus.

This review examines evidence relating environmental factors to the development of systemic lupus erythematosus (SLE). The strongest epidemiologic evidence exists for the associations of silica, cigarette smoking, oral contraceptives, postmenopausal hormone therapy and endometriosis, with SLE incidence. Recent studies have also provided robust evidence of the association between alcohol consumption and decreased SLE risk. There are preliminary, conflicting or unsubstantiated data that other factors, including air pollution, ultraviolet light, infections, vaccinations, solvents, pesticides and heavy metals such as mercury, are related to SLE risk. Biologic mechanisms linking environmental exposures and SLE risk include increased oxidative stress, systemic inflammation and inflammatory cytokine upregulation, and hormonal triggers, as well as epigenetic modifications resulting from exposure that could lead to SLE. Identifying the environmental risk factors related to risk of SLE is essential as it will lead to increased understanding of pathogenesis of this complex disease and will also make risk factor modification possible for those at increased risk.

Single-nucleotide polymorphisms of peroxisome proliferator-activated receptor-γ are associated with systemic lupus erythematosus in a Chinese Han population.

Evidence has indicated that peroxisome-proliferator activated receptor-γ (PPAR-γ) agonists could be used in the prevention and treatment of murine systemic lupus erythematosus (SLE). However, to our knowledge, just one previous study has focused on the association between PPAR-γ polymorphisms and SLE in humans. To investigate the association between PPAR-γ polymorphisms and SLE in a Chinese population and on additional gene-gene interaction between multiple single nucleotide polymorphisms (SNPs) in PPAR-γ. Three SNPs of PPAR-γ were selected for genotyping in this case-control study: rs1805192, rs10865710 and rs709158. Logistic regression was used to examine the association between the three SNPs and SLE, and the odds ratio (OR) and 95% CI were calculated. Generalized multifactor dimensionality reduction (GMDR) was used to investigate additional interaction. All genotypes were distributed according to Hardy-Weinberg equilibrium. Logistic regression analysis showed a significant association between genotypes of rs1805192 variants and decreased SLE risk, after adjustment for sex, age, smoking, high-fat diet, low-fibre diet, alcohol status, body mass index and waist circumference. Participants with Ala allesles had a lower SLE risk than those homozygous for the wild-type allele (OR=0.78; 95% CI 0.69-0.92). GMDR analysis indicated that there was a significant two-locus model (P=0.001) involving rs1805192 and rs10865710, indicating a potential gene-gene interaction between them. Overall, the two-locus models had a cross-validation consistency of 10 out of 10 and a testing accuracy of 60.72%. There was a significant association between PPAR-γ rs1805192 genotypes and decreased SLE risk, and a potential gene-gene interaction between rs1805192 and rs10865710.

Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus

ObjectiveWe examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.Methods436 individuals who reported having a relative with SLE...