Interleukin-21 Polymorphism Affects Gene Expression and is Associated with Risk of Ischemic Stroke

There has been more and more evidence to confirm the essential role of inflammatory processes in the development of ischemic stroke. Interleukin-21 (IL-21), the most recently discovered CD132-dependent cytokine, plays a key role in regulating inflammation. The aim of the study was to understand the association between IL-21 polymorphisms and ischemic stroke, and the effects of these polymorphisms on gene expression. Two polymorphisms in IL-21, rs907715G/A and rs4833837A/G, were identified in 278 ischemic stroke patients and 282 healthy controls. Results showed that frequencies of rs907715GA and AA genotypes were significantly increased in cases than in controls (odd ratio (OR)?=?1.49, 95 % confidence interval (CI): 1.01–2.14, P?=?0.042; OR?=?2.21, 95 % CI: 1.38–3.53, P?=?0.001). Similarly, rs907715A allele revealed a positive association with the disease (OR?=?1.52, P?=?0.001). The rs4833837A/G polymorphism did not show any correlation with ischemic stroke. We further evaluated IL-21 messenger RNA (mRNA) and protein levels in peripheral blood mononuclear cells (PBMCs) from subjects carrying different polymorphism genotypes. Results revealed that subjects carrying polymorphic rs907715GA and AA genotypes had significantly higher IL-21 mRNA levels, whereas protein level was increased only in subjects with rs907715AA genotype. Serum level of IL-21 was also significantly elevated in subjects with rs907715AA genotype. These data suggest that IL-21 polymorphism is associated with increased susceptibility to ischemic stroke possibly by upregulating gene expression.     

Emerging Role of SIGIRR rs7396562(T/G) Polymorphism in Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease, with heterogeneous presentation. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs7396562, of the interferon induced with single immunoglobulin IL-1-related receptor (SIGIRR) gene with SLE in a Chinese population. A total of 741 SLE patients and 731 healthy control subjects were enrolled in the present study. The genotyping of polymorphism (rs7396562) was determined by TaqMan allele discrimination assay on the 7,300 real-time polymerase chain reaction system. The frequency of T allele for rs7396562 in patients was significantly higher than in controls (T versus G, OR?=?1.318, 95 % confidence interval (CI)?=?1.139–1.525, P?P?versus GG, P?=?0.002; TT versus TG?+?GG, P?=?0.002). We also analyzed the association of the SIGIRR rs7396562 T allele with clinical features; luckily, photosensitivity and malar rash had some significant signal with the SNP. In conclusion, our study represents the first report demonstrating an association of the SIGIRR rs7396562 polymorphism with SLE susceptibility in a Chinese population.     

Associations between PXK and TYK2 polymorphisms and systemic lupus erythematosus: a meta-analysis

Objective

The aim of this study was to determine whether phox homology domain containing serine/threonine kinase (PXK) and tyrosine kinase 2 (TYK2) confer susceptibility to systemic lupus erythematosus (SLE).

Materials and methods

The authors conducted meta-analyses on associations between SLE susceptibility and the rs6445975 polymorphism of PXK and the rs2304256, rs12720270, rs280519, and rs1272036 polymorphisms of TYK2.

Results

A total of 13 separate comparisons studies were included in this meta-analysis. Meta-analysis identified an association between SLE and the 2 allele of the rs6445975 polymorphism in the overall population [odds ratio (OR)?=?1.151, 95?% confidence interval (CI)?=?1.086–1.291, P?=?1.8E?06]. Stratification by ethnicity identified a significant association between this polymorphism and SLE in Europeans (OR?=?1.198, 95?% CI?=?1.118–1.285, P?=?3.4E?07), but not in Asians. Meta-analysis identified a significant negative association between SLE and the 2 allele of the rs2304256 polymorphism in the overall population (OR?=?0.808, 95?% CI?=?0.659–0.990, P?=?0.040), and a significant negative association was found in Europeans, but not in Asians.

Conclusions

This meta-analysis shows that the rs6445975 polymorphism of PXK and the rs2304256 polymorphism of TYK2 are associated with the development of SLE in Europeans.     

Association of STAT4 rs7574865 with Susceptibility to Systemic Lupus Erythematosus in Iranian Population

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disease with complex genetic inheritance that affecting different organs and systems. STAT4 has been newly identified as a susceptible gene in the development of SLE. According to recent studies, STAT4 has been associated with SLE in various populations. We investigated whether STAT4 single nucleotide polymorphisms (SNPs) were associated with susceptibility and clinical features of SLE in Iranian patients. The study group comprised 280 patients with SLE and 281 sex-, age-, and ethnicity-matched healthy controls of Iranian ancestry. Two SNPs (rs7574865 and rs7601754) were genotyped using the TaqMan MGB Allelic Discrimination method. Our results showed a significant association betweenrs7574865 T allele (odds ratio (OR)?=?1.50, 95 % CI?=?1.18–1.92, P?=?0.002) and susceptibility to SLE. The rs7574865TT genotype (P?=?0.02, OR?=?1.94, 95 % CI?=?1.74–3.19) and GT genotype (P?=?0.008, OR?=?1.71, 95 % CI?=?1.19–2.45) showed a significant association with the risk of SLE in the Iranian population. We concluded that STAT4 rs7574865 is associated with SLE susceptibility in the Iranian population and this SNP might be a factor in the pathogenesis of SLE. However, further studies are required to investigate the mechanism by which polymorphisms in this gene lead to SLE.     

The relevance of Tim-3 polymorphisms and F protein to the outcomes of HCV infection

Hepatitis C virus (HCV) is one of the major causes of liver inflammation. The aim of this study was to investigate the associations of T-cell immunoglobulin and mucin domain-3 (Tim-3) polymorphisms and the alternate reading frame protein (F protein) with the outcomes of HCV infection. Three single-nucleotide polymorphisms (SNPs; rs10053538, rs12186731, and rs13170556) of Tim-3 were genotyped in this study, which included 203 healthy controls, 558 hepatitis C anti-F-positive patients, and 163 hepatitis C anti-F-negative patients. The results revealed that the rs12186731 CT and rs13170556 TC and CC genotypes were significantly less frequent in the anti-F-positive patients [odds ratio (OR)?=?0.54, 95 % confidence interval (CI)?=?0.35–0.83, p?=?0.005; OR?=?0.26, 95 % CI?=?0.18–0.39, p?<?0.001; and OR?=?0.19, 95 % CI?=?0.10–0.35, p?<?0.001, respectively), and the rs13170556 TC genotype was more frequent in the chronic HCV (CHC) patients (OR?=?1.70, 95 % CI?=?1.20–2.40, p?=?0.002). The combined analysis of the rs12186731 CT and rs13170556 TC/CC genotypes revealed a locus-dosage protective effect in the anti-F-positive patients (OR?=?0.22, 95 % CI?=?0.14–0.33, p _trend?<?0.001). Stratified analyses revealed that the frequencies of the rs12186731 (CT?+?TT) genotypes were significantly lower in the older (OR?=?0.31, 95 % CI?=?0.15–0.65, p?=?0.002) and female (OR?=?0.30, 95 % CI?=?0.17–0.52, p?<?0.001) subgroups, and rs13170556 (TC?+?CC) genotypes exhibited the same effect in all subgroups (all p?<?0.001) in the anti-F antibody generations. Moreover, the rs13170556 (TC?+?CC) genotypes were significantly more frequent in the younger (OR?=?1.86, 95 % CI?=?1.18–2.94, p?=?0.007) and female (OR?=?2.38, 95 % CI?=?1.48–3.83, p?<?0.001) subgroups of CHC patients. These findings suggest that the rs12186731 CT and rs13170556 TC/CC genotypes of Tim-3 provide potential protective effects with the F protein in the outcomes of HCV infection and that these effects are related to sex and age.     

Association study of interleukin-19 rs2243188 polymorphism with systemic lupus erythematosus in a Chinese population

Abstract

The purpose of this study was to evaluate whether a single-nucleotide polymorphism (SNP), rs2243188 of interleukin-19 (IL-19), show significant evidence for association with SLE in a Chinese population. A total of 545 SLE patients and 613 healthy controls were collected in the present study. The genotyping of IL-19 rs2243188 polymorphism was detected by TaqMan allele discrimination assay on the 7300 real time polymorphism chain reaction system. The minor C allele of rs2243188, relative to the major A allele, appeared to have a significantly lower frequency in SLE patients (31.0%) as compared with controls (35.5%) (χ²?=?5.19, p?=?0.023). We also discovered a statistical significance in the dominant model (CC?+?CA versus AA: OR?=?0.755, 95% CI?=?0.598–0.953, p?=?0.018). However, no significant difference in genotype distribution was found between SLE patients and controls (p?=?0.056). Furthermore, an increased frequency of CC genotype were also detected in lupus nephritis (LN) groups as compared with non-LN groups (p?=?0.024). Besides, the individuals with CC genotype had a 2.201-fold higher risk for the susceptibility to LN than those A allele carriers (AA?+?CA) (p?=?0.006). Unfortunately, the analyses on the relationship of IL-19 rs2243188 with several clinical manifestations of SLE failed to find any significant results. In conclusion, our observations suggested the minor C allele of SNP rs2243188 might be a protective factor for SLE in a Chinese Han population. Moreover, the subgroup analysis highlighted that IL-19 rs2243188 SNP was associated with the susceptibility to LN patients.     

Association Study of Common Genetic Variants in Pre-microRNAs in Patients with Ulcerative Colitis

Background

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population.

Methods

The rs11614913 (T?>?C), rs2910164 (C?>?G), and rs3746444 (A?>?G) SNPs were genotyped in 170 UC and 403 control subjects.

Results

The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)?=?1.51, 95% CI?=?1.03?C2.21, p?=?0.037). The rs3746444 AG genotype was associated with onset at an older age (OR?=?1.70, 95% CI?=?1.04?C2.78, p?=?0.035), left-sided colitis and pancolitis (left-sided colitis, OR?=?2.10, 95% CI?=?1.12?C3.94, p?=?0.024; pancolitis, OR?=?1.81, 95% CI?=?1.09?C3.01, p?=?0.028, left-sided colitis?+?pancolitis, OR?=?1.91, 95% CI?=?1.26?C2.92, p?=?0.003), higher number of times hospitalized (OR?=?2.63, 95% CI?=?1.22?C5.69, p?=?0.017), steroid dependence (OR?=?2.63, 95% CI?=?1.27?C5.44, p?=?0.014), and refractory phenotypes (OR?=?2.76, 95% CI?=?1.46?C5.21, p?=?0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2??, OR?=?0.36, 95% CI?=?0.17?C0.79, p?=?0.012), steroid dependence (OR?=?0.42, 95% CI?=?0.21?C0.88, p?=?0.021), and refractory phenotypes (OR?=?0.38, 95% CI?=?0.20?C0.72, p?=?0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C?+?C/C, OR?=?2.21, 95% CI?=?1.17?C4.18, p?=?0.016).

Conclusions

Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.     

Association of polymorphic variants of IL-1β and IL-1RN genes in the development of Graves’ disease in Kashmiri population (North India)

Purpose

Graves’ disease (GD) is a multigenic, organ specific autoimmune disorder with a strong genetic predisposition and IL-1β has been shown to be involved in its pathogenesis. The present study was aimed to determine the genetic associations between polymorphisms of IL-1β gene promoter region (?511?T>C) (rs16944), exon 5 (+3954 C>T) (rs1143634) and IL-1RN gene VNTR (rs2234663) polymorphism in patients with GD in ethnic Kashmiri population.

Association between the three functional miR-146a single-nucleotide polymorphisms,rs2910164, rs57095329, and rs2431697, and autoimmune disease susceptibility: A meta-analysis

Studies suggest associations between the miR-146a single nucleotide polymorphisms (SNPs) and susceptibility to autoimmune diseases. However, the results are inconsistent and inconclusive. Therefore, the aim of this study was to arrive at a conclusion about the association between the three functional miR-146a SNPs and autoimmune disease risk. Studies were identified through PubMed/MEDLINE searches for studies published up to January 2016 using as keywords rs2910164, rs57095329, rs2431697, and miR-146a polymorphisms. Thirty studies were included in the meta-analysis. The SNP rs2910164?G?>?C was found to be associated with increased risk of multiple sclerosis (CC?+?CG versus GG, OR = 1.25, 95% CI: 1.01–1.55), with decreased risks of psoriasis (C versus G, OR = 0.81, 95% CI: 0.69–0.96; CC versus GC?+?GG, OR = 0.73, 95% CI: 0.56–0.94), Behcet’s disease (CC versus GC?+?GG, OR = 0.60, 95% CI: 0.50–0.73), asthma (C versus G, OR = 0.80, 95% CI: 0.69–0.93; CC versus GC?+?GG, OR = 0.65, 95% CI: 0.48–0.86), and uveitis (CC?+?CG versus GG, OR = 0.61, 95% CI: 0.49–0.77). The SNP rs2431697 C?>?T was found to be associated with an increased risk of SLE (T versus C, OR = 1.26, 95% CI: 1.15–1.38; TC?+?TT versus CC, OR = 1.28, 95% CI: 1.03–1.58; TT versus TC?+?CC, OR = 1.40, 95% CI: 1.21–1.62). The SNP rs57095329 A?>?G was found to be associated with an increased risk of SLE (G versus C, OR = 1.25, 95% CI: 1.17–1.35). The miR-146a SNPs rs2910164, rs57095329, rs2431697 are associated with susceptibility to certain autoimmune diseases. However, for other autoimmune diseases, they may be protective or insignificant.     

Interleukin-6-174G > C (rs1800795) polymorphism distribution and its association with rheumatoid arthritis: A case-control study and meta-analysis

The association of interleukin-6 (IL-6)-174G?>?C (rs1800795) single nucleotide polymorphism (SNP) with the risk of acquiring rheumatoid arthritis (RA) is a relevant issue because of conflicting and consensus lacking reports published in literature. We investigated IL-6-174G?>?C promoter polymorphism in 34 RA patients, attending a tertiary care hospital in north India. We also performed a meta-analysis, of the previously published studies reporting this genetic relationship, in overall population, and independently in Asian and Caucasian ethnicities to further elucidate this association. A total of 13 studies, including the current one, involving 3291 RA cases and 3812 controls were analyzed. Out of the 13 studies, 6 were from Asian, 6 from Caucasian and 1 from a mixed population. Our case-control study showed significant association of IL-6-174G?>?C SNP with increased RA risk: allelic (OR?=?3.750, 95% CI?=?1.800–7.813, p?<?0.001); dominant (OR?=?2.800, 95% CI?=?1.167–6.721, p?=?0.021); and recessive (OR?=?36.72, 95% CI?=?2.004–672.7, p?=?0.015). The meta-analysis revealed the increased RA risk associated with IL-6-174G?>?C SNP in overall population: allelic (OR?=?1.650, 95% CI?=?1.169–2.329, p?=?0.004); homozygous (OR?=?1.380, 95% CI?=?0.906–2.101, p?=?0.133); heterozygous (OR?=?1.559, 95% CI?=?1.001–2.428, p?=?0.049); dominant (OR?=?1.663, 95% CI?=?1.078–2.567, p?=?0.022); and recessive (OR?=?1.366, 95% CI?=?0.964–1.935, p?=?0.079). Subgroup analysis also showed this polymorphism to be associated with increased RA risk in Asian population: allelic (OR?=?3.724, 95% CI?=?1.361–10.190, p?=?0.010); dominant (OR?=?3.823, 95% CI?=?1.320–11.074, p?=?0.013); and recessive (OR?=?4.357, 95% CI?=?1.634–11.623, p?=?0.003), but not in Caucasian population. This meta-analysis shows that IL-6-174G?>?C SNP is significantly associated with increased RA risk in overall, and specifically in Asian population.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

Impact of the IL-17F,IL-23 and IL-23R on susceptibility and phenotype of systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is a disease characterized by excessive proinflammatory cytokine production and damage to multiple organ systems. To investigate the potential association between cytokine gene polymorphisms and SLE, we performed a case-control study based on Polish population. SLE patients and controls, were examined for IL-23A rs11171806?G/A and IL-23R (rs1884444?G/T, rs10489629?G/A) by TaqMan SNP genotyping assay, for IL-17F rs763780 A/G and rs2397084A/G using the PCR– RFLP method. An increased frequency of AG genotype as well as G allele of the IL-17F rs763780 was found in patients with SLE, as compared with healthy subjects (OR?=?3.947; p?=?0.001 and OR?=?3.538; p?=?0.002, respectively). Frequencies of the rs1884444 TT genotype (OR?=?138.1) and the rs1884444 T allele (OR?=?2.176) were also higher in SLE patients (both p?0.0001). Overall, weak LD was observed between the IL-17F rs763780 A/G and rs2397084 A/G polymorphisms (D'-0.003, r² – 0.000). From four possible haplotypes, frequencies of AG showed differences between both examined groups (p?0.0001). We also observed a weak LD between the IL-23R rs10489629G/A and rs1884444?G/T (D'-0.199, r² –0.026). The genotype–phenotype analysis showed significant association between the IL-17F rs2397084 and mean value of the hemoglobin (p?=?0.01), the IL-17F rs763780 and age (p?=?0.008) and lupus anticoagulant (p?=?0.09), the IL-23 rs11171806 and urea (p?=?0.08) and C3 complement (p?=?0.03), and the IL-23R rs1884444?G/T and activated partial thromboplastin time (p?=?0.06). Present findings indicated that IL-17F rs763780 A/G and IL-23R rs1884444?G/T polymorphisms may be involved in susceptibility to SLE in the Polish population.     

Associations between interleukin-10 polymorphisms and susceptibility to psoriasis: a meta-analysis

Objective

The aim of this study was to determine whether three specific interleukin-10 (IL-10) polymorphisms confer susceptibility to psoriasis.

Methods

A meta-analysis was conducted on the associations between the IL-10-1082 G/A, -592 C/A polymorphisms and haplotypes of the IL-10-1082 G/A, -592 C/A, -819 C/T polymorphisms and psoriasis.

Results

A total of eight studies involving 1,018 psoriasis patients and 1,186 controls were considered in the meta-analysis. No association was found between psoriasis and the IL-10-1082 G allele in all study subjects [odds ratio (OR)?=?1.098, 95?% confidence interval (CI)?=?0.923?1.306, p?=?0.291] or between this allele and psoriasis in Europeans (OR?=?0.990, 95?% CI?=?0.809?1.214, p?=?0.925), but a significant association was found in Asians (OR?=?1.785, 95?% CI?=?1.144?2.76, p?=?0.011). Three polymorphisms at the promoter region of IL-10 (-1082 G/A, -819 C/T, -592 C/A) are known to be in complete linkage disequilibrium, but no association was found between the haplotype and psoriasis.

Conclusions

This meta-analysis shows that the IL-10-1082 G/A polymorphism confers susceptibility to psoriasis in Asians, and suggests that the IL-10 promoter -1082 polymorphism has an ethnicity-specific effect.     

Association Study of IFIH1 rs1990760 Polymorphism with Systemic Lupus Erythematosus in a Chinese Population

Systemic lupus erythematosus (SLE) is a complex autoimmune disease arising from the action of multiple genetic and environmental risk factors. The aim of this study was to examine the association of a single-nucleotide polymorphism, rs1990760, of the interferon induced with helicase C domain 1 (IFIH1) gene with SLE in a Chinese population. A total of 877 SLE patients and 978 healthy control subjects were enrolled in the present study. The genotype of the IFIH1 rs1990760 polymorphism was determined by Sequenom MassARRAY technology. The IFIH1 rs1990760 T allele was significantly increased in patient group compared with control subjects (T versus C, Odds ratio?=?1.20, 95 % confidence interval?=?1.02–1.40). However, no significant difference in genotype distribution was found between cases and controls (P?=?0.07). No significant evidence was detected for the association of the IFIH1 rs1990760 polymorphism with SLE under neither dominant nor recessive model (TT + TC versus CC, P?=?0.06; TT versus TC + CC, P?=?0.08). We also analyzed the association of the IFIH1 rs1990760 T allele with clinical features, whereas no significant signal was found. In conclusion, our study represents the first report demonstrating an association of the IFIH1 rs1990760 polymorphism with SLE susceptibility in a Chinese population.     

PTPN22 1858C > T polymorphism and susceptibility to systemic lupus erythematosus: a meta-analysis update

Studies performed in the past years showed PTNP22 1858?C?>?T (rs2476601) polymorphism as associated with systemic lupus erythematosus susceptibility, although conflicting findings are still found. In this context, a powerful statistical study, such as meta-analysis, is necessary to establish a consensus. The aim of this study was to evaluate association studies between the PTPN22 1858?C?>?T polymorphism and SLE by a meta-analysis update, including three recently published studies in the last three?years. A total of 3868 SLE patients and 7458 healthy individuals were considered herein, enclosing 19 studies from Asian, American, European and Latin ethnic groups. Odds ratio (OR) was performed for allelic, dominant and recessive genetic models. Statistically significant association was found between the PTPN22 1858?C?>?T polymorphism and susceptibility to SLE in all inheritance models. Allelic genetic model data (OR?=?1.54, 95% confidence interval (CI)?=?1.38–1.72, p value=.000) shows that T allele confers increased SLE susceptibility. As well as recessive genetic model (OR?=?2.04, 95% CI?=?1.09–3.82, p value?=?.030) for T/T genotype. Instead, dominant genetic model shows that C/C genotype confers lower susceptibility for SLE development (OR?=?0.62, 95% CI?=?0.54–0.72, p value?=?.000). In addition, we provided an ethnicity-derived meta-analysis. The results showed association in Caucasian (OR?=?1.47, p value?=?.000) and Latin (OR?=?2.41, p value?=?.000) ethnic groups. However, rs2476601 polymorphism is not associated nor in Asian (OR=?1.31; p value?=?.54) and African (OR?=?2.04; p value=.22) populations. In conclusion, present meta-analysis update confirms that T allele and T/T genotype in PTPN22 1858?C?>?T polymorphism confers SLE susceptibility, particular in Caucasian and Latin groups, suggesting PTPN22 1858?C?>?T as a potential genetic marker in SLE susceptibility.     

Association of Toll-Like Receptor 4 Polymorphisms with Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Toll-like receptor 4 (TLR4) is a critical mediator of innate immunity. Polymorphisms in TLR4 gene have been shown to be associated with impaired inflammatory response. Here, we investigated the association of TLR4 polymorphisms with T2DM. Four TLR4 polymorphisms (+986A/G, +1196C/T, +3725G/C, and +11367G/C) were genotyped in a total number of 822 T2DM patients and 835 healthy controls. Results showed that the +986A/G and +1196C/T polymorphisms did not exist in the Han Chinese population. The prevalence of TLR4 +3725GC and CC genotypes were significantly decreased in T2DM cases than in controls (odds ratio (OR)?=?0.62, 95 % confidence interval (CI)?=?0.50–0.78, p?=?3.48?×?10^?5, and OR?=?0.36, 95 % CI?=?0.22–0.59, p?=?1.55?×?10^?5, respectively). Also, the frequency of TLR4 +3725C allele was significantly lower in T2DM patients (p?=?2.46?×?10^?9). When analyzing the TLR4 +11367G/C polymorphism, the +11367CC genotype revealed lower numbers in patients compared to healthy controls (OR?=?0.46, 95 % CI?=?0.27–0.78, p?=?0.0032). Analysis of the clinical features on the control subjects demonstrated no correlations between these TLR4 polymorphisms and sex, age, body mass index, etc. (p?>?0.05). In conclusion, these data indicate that TLR4 +3725G/C and +11367G/C polymorphisms may be novel protective factors against T2DM in the Chinese population.     

Interleukin-7 Receptor Single Nucleotide Polymorphism rs6897932 (C/T) and the Susceptibility to Systemic Lupus Erythematosus

Emerging evidences were accumulated to support the view that aberrant interleukin-7 (IL-7) signaling might be associated with autoimmunity. Former studies demonstrated the single nucleotide polymorphism (SNP) rs6897932 C/T in the IL-7 receptor (IL-7R) gene was associated with susceptibility to autoimmune diseases, including multiple sclerosis and type I diabetes. Given these, this study was conducted to investigate whether an association existed between SNP rs6897932 and the susceptibility to systemic lupus erythematosus (SLE), a severe systemic autoimmune disease. In this context, 816 SLE patients and 816 controls from a Chinese population were recruited for this study, and the results showed that the major allele C of rs6897932 showed a higher frequency in SLE patients compared with controls (P?=?0.039, C versus T); significant difference was also detected under a recessive model with regard to the distribution of genotype frequencies between SLE patients and controls (P?=?0.041, CC versus CT + TT), which was not consistent with the results under a dominant model (P?=?0.349, CC + CT versus TT). Moreover, association studies were also performed contraposing the relationship between the SNP rs6897932 C/T and lupus nephritis as well as 10 clinical features of SLE; however, no significant association signal was found regarding the distribution of allele and genotype frequencies between SLE patients positive and negative for the presence of 11 sub-phenotypes. In conclusion, the major allele C of SNP rs6897932 may be associated with increased SLE risk in Chinese populations, and further studies are still encouraged to shed light on the true associations between SLE and its susceptibility genes with respect to IL-7R gene.     

IL21 and IL21R polymorphisms and their interactive effects on serum IL-21 and IgE levels in patients with chronic hepatitis B virus infection

Interleukin (IL)-21 may affect both T-cell and B-cell responses and was suggested to be involved in response to HBV infection. This study explored IL21rs907715 and rs2221903 and IL21R T-83C and rs3093301 polymorphisms and serum IL-21 and IgE levels in 395 patients with chronic HBV infection, 75 HBV infection resolvers and 174 healthy controls. IL21R T-83C was not polymorphic in the study populations. IL21 rs2221903 AG was less frequent in HBV patients than in resolvers (p < 0.001, OR = 0.364, 95% CI = 0.211–0.629) or in controls (p = 0.017, OR = 0.589, 95% CI = 0.381–0.911). IL21R rs3093301 TT was more frequent in HBV patients than in controls [p value after Bonferroni correction (p_c) = 0.022, OR = 1.908, 95% CI = 1.158–3.142] and more frequent in resolvers than in controls (p_c = 0.010, OR = 2.965, 95% CI 1.375–6.392). The carriage of IL21 rs2221903 AG/IL21R rs3093301 CT + IL21 rs2221903 AG/IL21R rs3093301 TT was less frequent in patients than in resolvers (p_c = 0.007, OR = 0.236, 95% CI = 0.096–0.579) and more frequent in resolvers than in controls (p_c = 0.014, OR = 4.354, 95% CI = 1.660–11.420). IL21 rs2221903 was, by interaction with IL21R rs3093301, associated with serum IL-21 and IgE levels in HBV patients. It is suggested that IL21 rs2221903 and IL21R rs3093301 polymorphisms may, independently or interactively, affect the susceptibility to and/or persistence of HBV infection potentially through altering IL-21 and IgE production.     

Autophagy Gene Polymorphism is Associated with Susceptibility to Leprosy by Affecting Inflammatory Cytokines

Autophagy and inflammation closely interact with each other, and together, they play critical roles in bacterial infection. Leprosy is caused by the infection of Mycobacterium leprae (M. leprae). The objective of the study was to investigate the association between polymorphisms in IRGM, an autophagy gene, and susceptibility to leprosy, and identify possible functions of the polymorphism in the infection of M. leprae. Two polymorphisms in IRGM, rs4958842 and rs13361189, were tested in 412 leprosy cases and 432 healthy controls. Levels of inflammatory cytokines including interleukin 1 beta, IL-4, IL-6, and interferon gamma (INF-γ) were measured after the infection of M. leprae in the peripheral blood mononuclear cell (PBMC) of subjects with different genotypes of rs13361189. Data showed that prevalence of rs13361189TC and CC genotypes were significantly higher in leprosy patients than in healthy controls (odds ratio (OR)?=?1.49, 95 % confidence interval (CI) 1.09–2.04, P?=?0.012; OR?=?2.58, 95 % CI 1.65–4.05, P?<?0.001; respectively). Furthermore, the frequency of rs13361189CC genotype was increased in patients with complications than those without complications (P?=?0.011). When analyzing the effect of rs13361189 polymorphism on M. leprae infection, we identified that M. leprae-infected PBMC with rs13361189CC genotype expressed significantly elevated levels of INF-γ and IL-4 than those with TT genotype. Our results suggested autophagy gene polymorphism was associated with the increased risk of leprosy by affecting inflammatory cytokines.