Matrix Metalloproteinase-9 rs17576 Gene Polymorphism and Behçet’s Disease: Is There an Association?

Background: Clinical studies have reported a significant association between matrix metalloproteinases (MMP), particularly (MMP-9), and inflammatory diseases including Behçet’s disease (BD).

Purpose: To study the relationship between MMP-9 rs17576 gene polymorphism and the development of BD, and its relation to disease activity among Egyptian patients.

Methods: A total of 100 BD patients and 100 healthy control volunteers were genotyped for MMP-9 rs17576 polymorphism with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), followed by the confirmation of our results in random subgroups using direct DNA sequencing technique.

Results: The frequency of the GG genotype and G allele was significantly higher in BD patients as compared to the normal controls (p = 0.011, OR 8.61; p = 0.03, OR 1.65, respectively). There was no significant association between the MMP-9 rs17576 polymorphism and the clinical outcomes of BD.

Conclusion: our study suggests a significant association of the MMP-9 rs17576 A/G polymorphism with increased risk of BD development in Egyptian patients.     

PTPN22 Single-Nucleotide Polymorphisms in Iranian Patients with Type 1 Diabetes Mellitus

Background: PTPN22 plays a crucial role in regulating the function of various cells of the immune system, particularly T cells. Polymorphisms of the PTPN22 gene have been associated with many autoimmune diseases, including type 1 diabetes (T1D) which is a T-cell-mediated disease.

Objective: The present study was aimed at genotyping of an Iranian population for five polymorphisms of the PTPN22 gene.

Methods: The study population consisted of 99 T1D patients and 100 healthy controls. We genotyped five single-nucleotide polymorphisms (SNPs) (rs12760457, rs1310182, rs1217414, rs33996649, and rs2476601) of the PTPN22 gene.

Results: Regarding the variant rs2476601, genotypes AG and GG were increased and decreased in T1D patients compared with controls, respectively. Further, alleles G and A of this SNP were found to be decreased and increased in T1D patients, respectively (p value = 0.001). However, T1D and control groups did not differ on genotype distribution or allele frequency for other investigated SNPs.

Conclusions: The PTPN22 rs2476601 minor allele (A) was associated with T1D in Iran, accounting for its pathophysiology in autoimmune diseases.     

Reduction in CD16/CD56 and CD16/CD3/CD56 Natural Killer Cells in Coronary Artery Disease

Background: Natural killer (NK) cells are the potential modulators of inflammatory reactions that exert several unique biological effects and could lead to future adverse events of coronary artery disease (CAD).

Hypothesis: The purpose of this study was to find out the possible association of modulation in NK cell, TNK cells, T cells, B cells, and tumor necrosis factor alpha (TNF-α) in CAD patients and various forms of myocardial infarction.

Methods: The present study included total 190 subjects (98 confirmed CAD patients both men and women and 92 healthy control individuals). Serum concentration of TNF-α was measured by ELISA method. For the measurement of various immune cells, viz., NK cell, TNK cells, T cells, and B cells, flow-cytometric analysis was performed.

Results: A significant reduction by 15% (P < 0.001) in CD16/CD56 NK cells was observed in CAD patients. Moreover, non-ST segment elevation myocardial infarction (NSTEMI), ST segment elevation myocardial infarction (STEMI), unstable angina (UA), and combined UA + NSTEMI group also showed a significant decline in NK cells compared with control individuals. CD16/CD56/CD3 TNK cells showed a significant reduction in CAD, NSTEMI, STEMI, and UA categories. However, UA + NSTEMI group did not show any significant change in TNK cells. On the other hand, the level of TNF-α was found to be significantly elevated in CAD, STEMI, and UA groups. NSTEMI and combined UA + NSTEMI group did not show any significant change in TNF-α level.

Conclusion: Current study provides an insight toward the association of immune cells and inflammation with CAD.     

Complex role of IL-23R polymorphisms on ankylosing spondylitis: a meta-analysis

Background: The aim of the meta-analysis was to evaluate the association between 10 widely studied polymorphisms of interleukin-23 receptor gene (IL-23R) and ankylosing spondylitis (AS).

Methods: A comprehensive literature search, screening of eligible articles and data extraction was performed independently by two investigators. Further meta-analysis was conducted with STATA 12.0 software (Stata Corp.; College Station, TX, USA). The association between IL-23R polymorphisms and AS was evaluated by odds ratio (OR) and 95% confidence intervals (95% CI).

Results: Twenty-five case–control studies with 8431 cases and 8972 controls were included in this meta-analysis. Quantitative meta-analysis revealed that minor allele frequency (MAF) of rs1004819, rs1495965, and rs2201841 was significantly higher in the AS group (p value < .001, < .001, = .010, respectively). MAF of rs10489629, rs11209026, rs11465804, and rs1343151was significantly lower in the AS group (p value = .002, < .001, = .032, < .001, respectively). However, there is no significant difference between these two groups in rs10889677, rs11209032, and rs7517847 frequency (p value = .128, .237, .131, respectively).

Conclusions: The present study indicates that minor allele carriers of rs1004819, rs1495965, and rs2201841 are susceptible to AS. Conversely, minor alleles of rs10489629, rs11209026, rs11465804, and rs1343151 have protective effect on AS.     

Efficacy and safety of SQ house dust mite (HDM) SLIT-tablet treatment of HDM allergic asthma

Introduction: In the treatment of house dust mite (HDM) respiratory allergic disease, allergy immunotherapy constitutes an add-on treatment option targeting the underlying immunological mechanisms of allergic disease. However, for the treatment of HDM allergic asthma, the use of subcutaneous allergy immunotherapy (SCIT) has been limited by the risk of systemic adverse events. Thus, sublingually administered allergy immunotherapy (SLIT) has been investigated as a treatment option with an improved tolerability profile that allows for safer treatment of patients with HDM allergic asthma.

Areas covered: In this Drug Profile, we provide a review of the clinical data behind the SQ HDM SLIT-tablet, which was recently approved for the treatment of HDM allergic asthma and allergic rhinitis by regulatory authorities in several European countries.

Expert commentary: The SQ HDM SLIT-tablet is the first allergy immunotherapy to be tested prospectively in patients with asthma, and to favorably modify patient relevant end points such as requirement for inhaled corticosteroid (ICS) or the time to first asthma exacerbation upon ICS reduction, suggesting that SQ HDM SLIT-tablet treatment may contribute to improving overall asthma control.     

Lack of Association between MYO9B Gene Polymorphisms and Susceptibility to Coeliac Disease in Caucasians: Evidence from a Meta-Analysis

Objective: Coeliac disease (CD) is a complex disorder influenced by environmental and genetic factors. Recently, a number of studies reported MYO9B gene is associated with CD, but the results are controversial. The aim of this study is to clarify this dispute by means of a meta-analysis.

Methods: The databases of PubMed, Web of Science, and Embase updated to August 2015 were retrieved. Crude odds ratio (OR) and corresponding 95% confidence interval (95%CI) as effect size were calculated by fixed or random effect model according to the heterogeneity.

Results: A total of 8 studies including 2272 cases and 5419 controls were enrolled in this meta-analysis. There was no significant association both in allele and genotype comparisons between the MYO9B (rs2305764, rs2305767, rs1457092) polymorphism and CD in Caucasian populations. No publication bias was detected in this meta-analysis.

Conclusions: This meta-analysis indicates that MYO9B gene polymorphisms might be not associated with CD susceptibility in Caucasians. Further studies are still needed for definitive conclusions.     

Pregnane X Receptor Polymorphisms and Risk of Inflammatory Bowel Disease: A Meta-Analysis

Background: Pregnane X receptor (PXR) gene polymorphisms have been widely studied in terms of the association with inflammatory bowel disease (IBD), with inconsistent results.

Objective: The present meta-analysis was performed to assess the association between PXR gene polymorphisms and the susceptibility of IBD, Crohn’s disease (CD), and ulcerative colitis (UC).

Methods: PubMed, Wanfang, and CNKI databases were searched for eligible studies before November 1, 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to calculate the various genetic models using either a fixed-effect or a random-effect model. The heterogeneity of the included studies was examined with Cochran Q and I² statistics. Begg’s rank correlation test and Egger’s linear regression test were used to assess the publication bias.

Results: A total of six studies with 4248 cases and 3853 controls were included in this meta-analysis. Three PXR gene polymorphisms were evaluated: rs1523127, rs2276707, and rs6785049. Our analyses of rs1523127, rs2276707, and rs6785049 suggested that PXR gene polymorphism had no obvious influence on the risk of IBD in Caucasians. Subgroup analyses based on disease type showed similar results.

Conclusion: Our meta-analysis revealed that PXR gene polymorphism may not be significantly associated with IBD susceptibility. However, the number of original studies was limited and further studies with large samples are needed to verify the results.

Abbreviations: PXR = pregnane X receptor, IBD = inflammatory bowel disease, CD = Crohn’s disease, UC = ulcerative colitis, ORs = pooled odds ratios, 95% CIs = 95% confidence intervals, NOS = Newcastle–Ottawa scale, HWE = Hardy–Weinberg equilibrium.     

Interferon Regulatory Factor 5 Gene Polymorphisms in Iranian Women with Unexplained Recurrent Pregnancy Loss

Objective: This study aimed to examine the association of three functional IRF5 rs10954213, rs3757385, and rs41298401 polymorphisms with susceptibility to unexplained recurrent pregnancy loss (RPL) among Iranian women from south of Iran.

Methods: 176 women with unexplained RPL and 173 healthy postmenopausal controls were enrolled in this case-control study. Genotyping of the polymorphisms rs10954213 and rs3757385 was carried out using touchdown tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS PCR), and polymorphism rs41298401 was typed using PCR-restriction fragment length polymorphism (PCR-RFLP).

Results: Genotype frequencies were significantly different between RPL cases and controls regarding AG heterozygote genotype of rs10954213, GT genotype of rs3757385, and GG genotype of rs41298401. In addition, allele variants (G for rs10954213, T for rs3757385, and G for rs41298401) showed protective role against RPL, while GG haplotype of two first variants was shown to be a susceptibility factor for the disease.

Conclusion: These data provide the first evidence, to our knowledge, of the protective role of the studied IRF5 gene polymorphisms against unexplained RPL among Iranian women from south of Iran.     

VDR polymorphisms are associated with bone mineral density in post-menopausal Mayan-Mestizo women

Background: Osteoporosis is characterized by low bone mineral density (BMD), which is determined by an interaction of genetic, metabolic and environmental factors.

Aim: To analyse the association between two polymorphisms of VDR as well as their haplotypes with BMD in post-menopausal Maya-Mestizo women.

Subjects and methods: This study comprised 600 post-menopausal Maya-Mestizo women. A structured questionnaire for risk factors was applied and BMD was assessed at the lumbar spine (LS) and total hip (TH) by dual-energy X-ray absorptiometry. DNA was extracted from blood leukocytes. Two single-nucleotide polymorphisms of VDR (rs731236 and rs2228570) were studied using real-time PCR allelic discrimination for genotyping. Differences between the means of the BMDs according to the genotype were analysed with covariance. Haplotype analysis was conducted.

Results: TT genotype of rs731236 of VDR had higher BMD at total hip and femoral neck (FN), and one haplotype formed by the two polymorphisms was associated with only TH-BMD variations. This difference was statistically significant after adjustment for confounders. The genotype of rs2228570 of VDR analysis showed no significant differences with BMD variations.

Conclusion: The results showed that the TT genotype of rs731236 of VDR and one haplotype formed by rs731236 and rs2228570 polymorphisms were associated with higher BMD at TH and FN.     

Thymidylate synthase enhancer region: Novel allele in Indians

Background: Thymidylate synthase (TS) is the major target for fluoropyrimidine drugs like 5-Fluorouracil (5-FU). There are polymorphic tandem repeats in the TYMS gene enhancer region (TSER). The number of tandem repeats varies in different populations. The aim of this study was to determine the frequencies of the TSER tandem repeats (rs34743033) and compare the observed frequencies with those of other populations.

Methods: This study genotyped 350 healthy individuals by Polymerase Chain Reaction (PCR).

Results: A novel allele *1 (only a single repeat) was observed in four individuals, the individuals were heterozygous (TSER*1/*2) for TYMS. Another variant rs2853542 affecting the expression of Thymidylate synthase was also analysed. The observed genotype frequencies were compared with frequencies observed in other populations for understanding differences between various population groups. There was a statistically significant difference between Indians and Chinese, Kenyans, Ghanians, African-Americans, Americans of European Ancestry, British, Hungarians, Turkish, Australians and Brazilians.

Conclusion: This study identified a novel single repeat in the TYMS gene which might have an impact on the expression of this gene, which needs to be confirmed by functional studies.     

IL12 Gene Polymorphism in Association with Hepatocellular Carcinoma in HCV-infected Egyptian Patients

Background: Hepatocellular carcinoma has been recorded the commonest cancer in Egypt. This increasing incidence may be attributed to the high prevalence of hepatitis C virus with its complications, so this study aimed to investigate the association between the potentially functional polymorphisms of IL12A and IL12B genes as a risk factor of development of hepatocellular carcinoma (HCC) on top of hepatitis C virus (HCV) infection in an Egyptian population.

Materials and methods: We genotyped two loci of IL12 which were rs568408 (3’UTR G>A) for IL12A and rs3212227 (3’UTR A>C) for IL12B in 78 patients with HCC on top of chronic HCV infection. In addition, 64 cancer-free chronic HCV patients were studied, besides 92 healthy subjects who were included as control.

Results: Study of rs568408 (G>A) gene polymorphism showed that the A allele is higher while the G allele is lower in HCC cases than cancer-free chronic HCV patients (p = 0.006*). The A-containing genotypes AG and (AG+AA) were higher while the GG was lower (p = 0.009* and p = 0.005*), respectively. The study of the rs3212227 (A>C) polymorphism showed neither statistically significant differences between the C and A allele (p = 0.2) nor between CC, AC, or AC+CC in HCC cases and cancer-free chronic HCV patients (p = 0.7, p = 0.2, and p = 0.29), respectively.

Conclusion: Our findings showed that IL12A rs568408 (G>A) polymorphism may contribute to the risk of HCC on top of chronic HCV infection, whereas that of IL12B rs3212227 (A>C) do not.     

Association of LXRα polymorphisms with obesity and obesity-related phenotypes in an Iranian population

Background: Obesity is a multifactorial disorder due to the complex interaction between genetic and environmental factors. Liver X receptor alpha (LXRα), encoded by the gene NR1H3, is involved in lipoprotein metabolism and its genetic variations may also play a role in the aetiology of obesity.

Aim: To assess the association of two NR1H3 polymorphisms (rs11039155 and rs2279238) and their haplotypes with obesity in an Iranian population.

Subjects and methods: A total of 447 unrelated subjects (including 206 overweight, 162 obese and 79 controls) were enrolled in the study and were genotyped by TaqMan assay using DNA from peripheral blood. The association of these two LXRα polymorphisms with the presence of obesity and overweight was assessed.

Results: There was no significant association between the two SNPs and obesity, even after adjustment for age and sex. By logistic regression using a dominant model, the odds ratios for obesity were: 1.32 (0.85–2.74) for rs11039155 and 0.77 (0.30--1.99) for rs2279238. Haplotype analyses identified three common haplotypes GC, GT and AC with frequency greater than 1%, but none of the haplotypes was associated with the risk of obesity.

Conclusions: This study revealed that there was no significant association between LXRα polymorphisms and the presence of obesity in an Iranian population and suggests that these two SNPs are not major contributors to obesity risk in this population.     

Genetic Polymorphism (rs329498) in the Pellino-1 Gene as Possible Predisposal Factor for Systemic Lupus Erythematosus in a Chinese Population

Objective: The purpose of this study was to analyze the association of two single nucleotide polymorphisms (SNPs) in Peli-1 gene with systemic lupus erythematosus (SLE) in a Chinese population.

Methods: We conducted a case–control study and a total of 738 SLE patients and 827 healthy controls were finally recruited. Peli-1 rs329498 and rs10496105 polymorphisms were specified from genomic DNA using TaqMan genotyping assay on Fluidigm 192.24 system.

Results: Allele contrast showed the minor allele C was associated with decreased risk for SLE when compared with the A allele (OR = 0.851, 95% CI = 0.737–0.983, p = 0.028). Significant difference was observed in genotype distribution of rs329498 polymorphism between lupus nephritis (LN) patients and non-LN patients (χ² = 8.18, p = 0.017). Furthermore, we also found a decreased frequency of the minor allele C in LN patients (29.2%) than in non-LN patients (37.7%) (χ² = 8.67, p = 0.003). Moreover, a significant difference was also detected under a dominant model with regard to the distribution of genotype frequencies between LN patients and non-LN patients (CC + AC vs. AA: OR = 0.632, 95% CI = 0.451–0.884, p = 0.007). Clinical features analysis showed a significant difference in the distribution of genotypic frequencies between patients with malar rash and patients without this feature (χ² = 6.63, p = 0.036). Unfortunately, we failed to find any significant results between Peli-1 gene rs10496105 and SLE susceptibility.

Conclusions: Our observations suggested that Peli-1 gene polymorphism rs329498 might contribute to SLE susceptibility in Chinese Han Population. Likewise, the rs329498 SNP was also associated with the clinical features LN and malar rash in SLE patients.     

Association between IL-33 Gene Polymorphisms (rs1929992, rs7044343) and Systemic Lupus Erythematosus in a Chinese Han Population

Objective: Interleukin-33 (IL-33) is a member of the IL-1 family, and previous studies found the single-nucleotide polymorphisms (SNPs) in the IL-33 gene was related to susceptibility to autoimmune diseases, including rheumatoid arthritis, ankylosing spondylitis and Behcet’s disease. To date, no study has discussed the potential association between IL-33 gene polymorphisms and systemic lupus erythematosus (SLE).

Methods: We conducted a case-control study including 371 SLE patients and 408 healthy controls to investigate the correlation between the SNPs of IL-33 gene (rs1929992, rs7044343) and SLE in a Chinese Han population.

Results: There was significantly lower expression of allele G for rs1929992 in SLE patients than that in controls (G versus A, P = 0.012, OR = 1.310, 95% CI: 1.060–1.624 after adjustment with sex). Similarly, genotype GG was associated with the susceptibility to SLE as compared with the AA genotype (P = 0.017, OR = 1.714, 95% CI: 1.101–2.669 after adjustment with sex). We also found statistical significance in the dominant model (GG+GA versus AA, P = 0.017, OR = 1.481, 95% CI: 1.074–2.044 after adjustment with sex). However, we found no strong evidence for the association of IL-33 rs7044343 polymorphism with SLE. Moreover, association studies were performed on the relationship between the IL-33 gene polymorphisms and lupus nephritis as well as nine clinical features of SLE, but there was no significant association regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of sub-phenotypes.

Conclusion: Our findings indicate that IL-33 rs1929992 polymorphism may be a potential biomarker for susceptibility to SLE.     

300 IR HDM tablet: a sublingual immunotherapy tablet for the treatment of house dust mite-associated allergic rhinitis

Introduction: The once-daily 300 index of reactivity (IR) house dust mite (HDM) tablet (Actair®; Stallergenes Greer, Antony, France/Shionogi & Co. Ltd., Osaka, Japan) is the first sublingual immunotherapy (SLIT) tablet to be approved for the treatment of HDM-induced allergic rhinitis.

Areas covered: This drug profile reviews the current body of evidence on the efficacy, safety and tolerability of the 300 IR HDM tablet, its pharmacodynamics, and its role in clinical practice.

Expert commentary: Data from its clinical development program demonstrate favorable efficacy and safety in adults and adolescents with HDM-induced allergic rhinitis, irrespective of mono- or polysensitization status, or the presence of comorbid mild asthma. The 300 IR HDM tablet is effective from as early as 2 months after treatment initiation, providing allergic symptom control and a reduction in the need for symptomatic medication, while improving health-related quality of life. Clinical efficacy is maintained for 1 year after treatment is stopped.     

Association of FAM167A-BLK rs2736340 Polymorphism with Susceptibility to Autoimmune Diseases: A Meta-Analysis

Objective: The purpose of this study is to evaluate the correlation between family with sequence similarity 167A-B lymphoid tyrosine kinase (FAM167A-BLK) rs2736340 polymorphism and autoimmune diseases.

Methods: Databases including PubMed, EMBASE, Chinese National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature database (CBM) and Chinese database, Wan Fang database were used in searching eligible studies from January 1, 1966 to October 2, 2015. The odds ratios (ORs) and their 95% confidence intervals (CIs) were pooled to estimate the strength of the association.

Results: A total of 25 studies with 30,217 patients and 44,754 controls were included in the meta-analysis. The overall results showed FAM167A-BLK rs2736340 T allele was a risk allele for autoimmune diseases (OR 1.36, 95% CI 1.28–1.44, p < 0.001). In the subgroup by ethnicities, the results suggested T allele was an increased risk in North America, Europe, and Asia (OR 1.33, 95% CI 1.10–1.60, p = 0.004; OR 1.26, 95% CI 1.22–1.31, p < 0.001; and OR 1.46, 95% CI 1.40–1563, p < 0.001, respectively), but not in Africa. Subgroup analysis in different genetic models (recessive, dominant, and additive) revealed significant association between rs2736340 and autoimmune diseases in Asia and North America, but not the recessive model in Europe or Africa, or the additive model in Africa. Stratification analysis by diseases suggested FAM167A-BLK rs2736340 had a positive association with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Kawasaki disease, primary Sjogren’s syndrome (pSS), primary antiphosholipid syndrome (APS), and myositis.

Conclusion: The current meta-analysis suggested that FAM167A-BLK rs2736340 polymorphism is associated with several autoimmune diseases.     

A study on the genetic polymorphisms of CYP3A5 among the Orang Asli in Malaysia using a next generation sequencing platform

Background: CYP3A5 is the predominant sub-family of biotransformation enzymes in the liver and the genetic variations in CYP3A5 are an important determinant of inter-individual and inter-ethnic differences in CYP3A-mediated drug disposition and response.

Aim: This study aims to investigate the genetic polymorphisms of CYP3A5 among the Orang Asli in Peninsular Malaysia using a next generation sequencing platform.

Methods: Genomic DNAs were extracted from blood samples of the three main Orang Asli tribes and whole-genome sequencing was performed.

Results: A total of 61 single nucleotide polymorphisms were identified and all the SNPs were located in introns except rs15524, which is in the 3’UTR, and 11 of these polymorphisms were novel. Two allelic variants and three genotypes were identified in the Orang Asli. The major allelic variant was the non-functional CYP3A5*3 (66.4%). The percentages of Orang Asli with CYP3A5*3/*3 (47.2%) and CYP3A5*1/*3 (38.1%) genotypes are more than twice the percentage of Orang Asli with CYP3A5*1/*1 (14.8%) genotype. Almost half of the Orang Asli harboured CYP3A5 non-expressor genotype (CYP3A5*3/*3).

Conclusions: The predominance of the CYP3A5 non-expressor genotype among the Orang Asli was unravelled and the findings in this study may serve as a guide for the optimisation of pharmacotherapy for the Orang Asli community.     

Association between CD226 polymorphism and soluble levels in rheumatoid arthritis: Relationship with clinical activity

Objective: To study the relation between CD226 rs763361 gene polymorphism and CD226 serum level and to evaluate their role in susceptibility and disease activity of RA in a cohort of Egyptian individuals.

Methods: The serum level of CD226 was measured using a suitable ELISA kit and the CD226 rs763361 gene polymorphism was typed by PCR-RFLP for 112 RA patients and 100 healthy controls.

Results: Significant association with RA was found with CD226 T allele (OR (95%CI) = 1.6 (1.04–2.4), P = 0.032), and higher CD226 serum level (P = 0.001). Higher CD226 levels were associated with higher ESR values (P = 0.035), positive CRP (0.048), increased number of tender joints (P = 0.045), and higher DAS score (P = 0.035). Serum CD226 is an independent risk factor for the prediction of RA (P = 0.001). No correlations were found between the serum level of CD226 and different CD226 genotypes and also between them and RA activity grades.

Conclusion: The CD226 T allele may be susceptibility risk factors for the development of RA and the higher serum level of CD226 may be involved in the pathogenesis of RA in Egyptian patients. The serum level of CD226 and not CD226 genotypes could be considered as an independent risk factor for the prediction of RA within healthy individuals and also for RA disease activity.     

Meta-analysis of the association of IL2RA polymorphisms rs2104286 and rs12722489 with multiple sclerosis risk

Background: The interleukin-2 receptor alpha (IL2RA) gene polymorphisms may be implicated in the genetic susceptibility to multiple sclerosis (MS). This meta-analysis aims to evaluate the relationship of the IL2RA polymorphisms rs2104286 and rs12722489 with MS risk in different populations.

Methods: Eligible association studies were identified through search in Pubmed, Medline, Web of Science, and Scopus (end of search: August 2017). Summary odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects or fixed-effects models. All statistical analyses were two-sided.

Results: Eleven studies including 8608 cases and 9061 controls evaluated rs2104286. The results demonstrated that the A allele of rs2104286 was associated with increased risk of MS in Caucasians (OR = 1.19, 95%CI: 1.13–1.25, p < 0.001) and Asians (OR = 1.25, 95%CI: 1.01–1.55, p = 0.041), respectively. Concerning rs12722489, six studies with 4259 cases and 5420 controls were eligible. We found that the C allele of rs12722489 was associated with elevated MS risk in Caucasians (OR = 1.20, 95% CI: 1.12–1.29, p < 0.001) but not in Asians (OR = 1.10, 95%CI: 0.75–1.63, p = 0.629). Statistical evidence from the Egger and Begg tests showed absence of publication bias. Sensitivity analysis showed that the results were stable.

Conclusion: Our meta-analysis suggests that the rs2104286 A allele is associated with increased MS risk in both Caucasians and Asians, whereas the rs12722489 C allele is associated with elevated MS risk in Caucasians but not in Asians.