Interferon-gamma (IFN-γ) intronic variant (rs2430561) is a risk factor for systemic lupus erythematosus: Observation from a meta-analysis

Abstract

Background The role of interferon-gamma (IFN-γ) in autoimmune disorders has been well documented. Elevated levels of IFN-γ are observed in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and are linked with disease severity. Single nucleotide polymorphism in the intronic region of the IFN-γ gene (+874 T>A rs2430561) has been associated with susceptibility to the development of RA and SLE; however, the reports remained contradictories. We conducted a meta-analysis using earlier published articles to reach a valid conclusion on the role of IFN-γ polymorphism (+874 T>A) in autoimmune diseases. Materials and methods Various online databases such as PubMed, Google Scholar, Science Direct, and Scopus were searched to find eligible reports for inclusion in the present analysis. Two independent authors extracted eligible studies and data. The meta-analysis was performed by comprehensive meta-analysis software (CMA) v.3.1. Trial sequential analysis was performed to test whether enough case-control studies have already been conducted worldwide to reach a valid observation. Results Six published reports on the role of IFN-γ +874 T>A in SLE and four in RA were found after searching various databases. However, out of those six studies in SLE, in one study, the distribution of genotypes was not following the hardy-Weinberg equilibrium. In RA, three studies were deviated out of four reports. Thus, a total of five studies comprising 1440 SLE patients and 1748 controls were considered for the present meta-analysis. Meta-analysis showed a significant association between IFN-γ +874 T>A variants with susceptibility to SLE (homozygous comparison: p = 0.036, OR = 1.592, heterozygous model: p = 0.042, OR = 1.507, dominant model: p = 0.002, OR = 1.309). Conclusions IFN-γ +874 T>A variant is associated with predisposition to SLE development.

Investigating the causal association between systemic lupus erythematosus and migraine using Mendelian randomization analysis

“…7,8 A recent metaanalysis showed that almost one third of patients with SLE have migraine. 9 Katsiari et al showed that migraine prevalence in patients with SLE did not differ compared to those without SLE, and they suggested that the increased migraine prevalence found previously could have been due to methodological weaknesses. 10 The current evidence is primarily based on observational studies and suffers from shortcomings such as reverse causality, small sample sizes, and confounding factors (such as the distributions of gender and age).…”

“…Previous studies have shown a higher prevalence of migraine in patients with SLE compared to the general population, suggesting a possible link between these two conditions 7,8 . A recent meta‐analysis showed that almost one third of patients with SLE have migraine 9 . Katsiari et al.…”

“…9 demonstrated that migraine affects approximately one third of individuals with SLE worldwide. Migraine occurs more commonly among patients with SLE compared to individuals without SLE.…”

Approach to the Patient With Headache

“…Certain conditions are associated with primary or secondary headaches, including thyroid disease, systemic lupus erythematosus, polycystic ovarian syndrome, and joint hypermobility disorders. [58][59][60][61] SOCIAL HISTORY. A standard social history reveals information about smoking, alcohol consumption, drug use, employment type and status, physical activity, and the home environment.…”

Causal association between systemic lupus erythematosus and the risk of migraine: A Mendelian randomization study

“…A subsequent case–control study confirmed that the incidence of migraine was higher in patients with SLE than in healthy controls (Tjensvoll et al., 2011). In addition, a recent meta‐analysis showed that approximately one‐third of patients with SLE worldwide suffered from migraine and that the incidence of migraine was higher in patients with SLE than in healthy controls (Sarangi et al., 2023).…”