Proinflammatory Cytokine Gene Polymorphisms in Irritable Bowel Syndrome

Introduction

Irritable bowel syndrome (IBS) is a multifactorial functional gastrointestinal disorder, characterized by recurrent abdominal pain and altered bowel habits. Proinflammatory cytokines can play an important role in intestinal inflammation, while their production is under genetic control.

Methods

This study was performed in a group of patients with IBS to analyze the genotype frequencies of a number polymorphic genes coding for proinflammatory cytokine (interleukin-6 (IL), tumor necrosis factor-alpha (TNF-α), and IL-1 group). Using polymerase chain reaction with sequence-specific primers method, the cytokine genes were amplified, and alleles and genotypes of 71 patients with IBS were detected on gel electrophoresis, and the results were compared with healthy control subjects.

Results

Results of the analyzed data showed that the frequencies IL-1R C allele at position Pst-I 1970 (P?=?0.017), IL-6 G allele at position ?174 (P?=?0.002), and TNF-α G allele at position ?238 (P?<?0.001) in the patient group were significantly higher than the control group. IL-6 GG genotype (?174) and TNF-α GG genotype (?238) in the patient group were also significantly overrepresented (P?<?0.001), while IL-6 CG genotype (?174) and TNF-α GA genotype (?238) were significantly decreased in the patients with IBS (P?<?0.001). The frequencies of IL-6 (?174, nt565) GG haplotype and TNF-α (?308, ?238) GG haplotype were also significantly higher in the patient group (P?<?0.001), whereas the frequencies of the haplotypes IL-6 CG and TNF-α GA were significantly decreased in the patients with IBS (P?<?0.001).

Conclusion

IL-6 and TNF-alpha proinflammatory cytokine gene polymorphisms could change individual susceptibility to IBS and might have a role in pathophysiology of disease.     

Significant Impact of IL-6 -174G/C but Inverse Relation with -634 C/G Polymorphism in Patients with Non-Small Cell Lung Cancer in Kashmiri Population

To study the possible role of proinflammatory interleukin 6 -174 G>C (rs 1800795) and -634 C>G (rs 1800796) polymorphism in the pathogenesis of non-small cell lung cancer (NSCLC). A total of 190 NSCLC patients and 200 healthy controls were evaluated for polymorphic analysis of -174 G/C and -634 C/G by PCR-RFLP followed by DNA sequencing. A significant association was observed in the genotypic and allelic distribution of IL-6 -174 G/C in the NSCLC group as compared to control group [OR?=?2.7 (1.77–4.11), p?<?0.0001]. Smokers with the -174C allele were found to be significantly associated with NSCLC (p?=?0.01), while 634C/G SNP showed an inverse relation [OR-0.4, p?<?0.0001]. The present investigation revealed a significant association of the IL6 -174 G/C gene promoter polymorphism with NSCLC, and thus, the IL-6 -174G/C genotype can be considered as one of the biological markers in the etiology of NSCLC.     

Interleukin-6 promotor gene polymorphisms and susceptibility to chronic hepatitis B virus in Egyptians

AimTo investigate the association between IL-6 polymorphisms (?174G/C, ?572G/C and ?597G/A) and susceptibility to chronic hepatitis B virus (CHB) infection.MethodTotal 108 subjects with CHB infection and 102 healthy controls were enrolled in this study. IL-6 (?174G/C) was genotyped using Mutagenically separated Polymerase Chain Reaction (MS-PCR) while sequence specific primers-PCR (SSP-PCR) was used for studying ?572G/C and ?597G/A. IL-6 plasma level was measured using Enzyme-linked immunosorbent assay (ELISA).ResultsA significant increase (P < 0.01, P < 0.01, P < 0.001) in ?174GG, ?572GC and ?597GA; respectively in the CHB group compared to control group, while ?572GG genotype was significantly decreased (P < 0.01) in CHB patients. A significant increase (p < 0.01, p < 0.01) in ?174 G and ?597A alleles was observed in the CHB patient group; respectively. GGA haplotype is significantly increased (P < 0.05) while GCA haplotype is significantly decreased (P < 0.001) in the patient group. A moderate linkage disequilibrium (LD) (D′ = 0.719, r² = 0.474; P < 0.001) between IL-6 (?572G/C and ?597G/A) was observed. A significant reduction (P < 0.01) in IL-6 plasma level in CHB patients compared to healthy controls (22.28 ± 1.93 versus 32.08 ± 2.41), which was negatively correlated (r = ?0.216; P < 0.01) with HBV infection.ConclusionsThis study pointed to the potential role of IL-6 (?174G/C, ?572 G/C and ?597G/A) gene polymorphisms in the susceptibility to HBV infection. Our results allow for only preliminary conclusions due to relatively small sample size. There is a need for further larger scale studies to fully examine the possible relationship between these cytokine gene polymorphisms and the development of CHB.     

CD38 Gene polymorphisms and susceptibility to B cell chronic lymphocytic leukemia

CD38 was suggested to be not only a prognostic marker but also a key element in the pathogenetic network underlying chronic lymphocytic leukemia (CLL). We aimed at determining whether polymorphisms of CD38 gene influence the risk of B-CLL and thus analyzed two potentially functional CD38 single nucleotide polymorphisms (SNPs), rs6449182 (184 C>G), and rs1800561 (418 C>T) using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based assays in a study including 70 B-CLL patients and 70 age- and gender-matched controls. Our results demonstrated that the homozygous mutant genotypes of the two studied SNPs (GG and TT) showed a significantly higher risk of B-CLL compared with the homozygous wild types (p value?<?0.001, OR?=?2.813, 95% CI?=?1.898–4.168 and p value?=?0.011, OR?=?2.250, 95%CI?=?1.707–2.96, respectively). In addition, G and T carriers had more advanced clinical stage (p value?<?0.001). Also, a significant association was demonstrated between higher proportions of CD38-positive cells and carriers of G and T alleles (p value?<?0.001). Our data suggest that the risk of B-CLL carcinogenesis may be influenced by CD38 SNPs [rs6449182 (184 C>G) and rs1800561 (418 C>T)].     

Effect of Interleukin-2 Level and Genetic Variants on Coronary Artery Disease

Inflammation plays important roles in the development of atherosclerosis and coronary artery disease (CAD). Interleukin-2 (IL-2) is a proinflammatory cytokine and induces proliferation of T cells. The aim of the study was to understand the effect of IL-2 on the development of CAD from genetic polymorphism perspective and serum level perspective. IL-2 ?330T/G and +114T/G polymorphisms were tested in 692 CAD cases and 723 healthy controls. IL-2 expression of these two polymorphisms was compared. Serum level of IL-2 in CAD patients and controls was analyzed. Data showed that prevalence of IL-2 ?330GG genotype was significantly increased in CAD than in controls (p?=?5.1?×?10^?6). Function analysis revealed that subjects carrying IL-2 ?330GG genotype had higher serum level of IL-2 than those with TG or TT genotypes (p?<?0.01). Serum level of IL-2 in the study subjects was further analyzed, and results showed that CAD patients had significantly increased IL-2 level than healthy controls (p?<?0.01). Also, cases with three vessels affected were observed to have higher IL-2 level than cases with one vessel affected (p?<?0.05). These data suggested IL-2 polymorphism could affect the susceptibility to CAD by elevating protein expression, and serum level of IL-2 may be closed correlated with the development and progression of this disease.     

CD38+CD8+ and CD38+CD4+ T Cells and IFN Gamma (+874) Polymorphism Are Associated with a Poor Virological Outcome

The main objective of the work was to evaluate the use of CD38 on T lymphocytes, IFNγ (+874 A/T), and IL-10 (?1082 A/G) polymorphisms in HIV-infected patients under antiretroviral (ARV) therapy. Sixty-one patients were selected at the outpatient clinic for HIV infection at the Hospital São José de Doenças Infecciosas, Fortaleza, Ceará, Brazil. The patients were classified into two groups, according to viral load after one year of ARV therapy. In the aviremic group (group I), a reduction of 35.5% of CD38+CD4+ T cells was observed (p = 0.02) and 49.3% of CD38+CD8+ T cells (p = 0.001). In the viremic group (group II), a reduction of 37.2% of CD38+CD4+ T cells (p = 0.067), and 21.4% of CD38+CD8+ T cells (p = 0.60) occurred. No association was found between IL-10 (?1082) polymorphism and the type of response to ARV therapy. Regarding the gene polymorphism on IFNγ (+874 T/A), 73.34% of group I and 33.3% of group II presented the AA genotype. The relative risk of the individuals carrying AA genotype or the A allele and not being able to suppress the viral load level after one year of ARV therapy was 3.44 (1.25–9.45; p = 0.014) or 2.35 (1.05–5.26; p = 0.027), respectively. Our data suggested that an augmented frequency of activated CD38+CD8+ T cells as well as the presence of the A allele of IFNγ polymorphism could contribute to a reduced virological suppression in patients under antiretroviral therapy.     

Interleukin 6(-174G/C) Variant and its Circulating Levels in Coronary Artery Disease Patients and Their First Degree Relatives

Interleukin-6 (IL-6) a pleiotropic cytokine is a central mediator of inflammation in the pathogenesis of coronary artery disease (CAD). Our aim is to evaluate the serum levels of IL-6 and C-reactive protein (CRP) and to analyze the IL-6 polymorphism in CAD patients and to identify the first-degree relatives (FDRs) at risk of the disease in comparison with healthy controls. Estimation of IL-6 levels by enzyme-linked immunosorbent assay (ELISA) and CRP by latex reagent kit method, and genotyping of IL6 gene variants ?174 (G>C) was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 600 subjects. IL-6 and CRP levels were significantly high in patients followed by FDRs compared to controls. The frequency of the IL-6 genotype was significantly different between cases, FDRs and controls and association of serum IL-6 levels with genotype found to be significant in CC genotype compared to GC and GG at p?<?0.01 in CAD patients and FDRs, while there is no significant difference observed in controls. The study shows the importance of inflammation in the pathogenesis of CAD and predicts the risk of future coronary events in healthy asymptomatic FDRs.     

Analysis of G(-174)C IL-6 polymorphism and plasma concentrations of inflammatory markers in patients with type 2 diabetes and peripheral arterial disease

AIMS: To determine whether the G(-174)C interleukin 6 (IL-6) polymorphism influences the development of peripheral arterial disease (PAD) in individuals with type 2 diabetes. This was investigated by comparing the distribution of G(-174)C genotypes between patients with type 2 diabetes and PAD (PAD+) and those with type 2 diabetes but without PAD (PAD-). Plasma concentrations of IL-6, fibrinogen, C reactive protein (CRP), and vascular endothelial growth factor (VEGF) were also compared in PAD+ and PAD- patients. METHODS: Blood samples were collected from 146 PAD+ and 144 PAD- patients. SfaNI was used to determine the G(-174)C genotype. Plasma concentrations of IL-6, fibrinogen, CRP, and VEGF were measured by an enzyme linked immunosorbent assay. RESULTS: The GG genotype was more common in PAD+ patients than in PAD- patients. PAD+ patients also had increased mean plasma concentrations of IL-6, fibrinogen, CRP, and VEGF compared with PAD- patients. Mean plasma concentrations of IL-6, fibrinogen, and CRP in both PAD+ and PAD- patients were higher in those with the GG genotype than in those with the GC or CC genotypes. In contrast, mean plasma concentrations of VEGF in PAD+ and PAD- patients were not significantly different between those with different G(-174)C genotypes. CONCLUSIONS: These results support a model in which the GG genotype promotes PAD development among individuals with type 2 diabetes by inducing increased release of IL-6. Higher concentrations of IL-6 among those with the GG genotype is associated with increased plasma concentrations of fibrinogen and CRP.     

A prospective study of genetic markers of susceptibility to infection and inflammation, and the severity, progression, and regression of coronary atherosclerosis and its response to therapy

Inflammation plays a key role in susceptibility to coronary atherosclerosis and response to therapy. A diverse array of factors modulates inflammation, including interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and CD14 receptors on the surface of macrophages. Genes encoding for inflammatory markers have variants that regulate their expression and are potential risk factors for atherosclerosis. We prospectively analyzed the possible association of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C variants, located in the promoter regions, with the severity, progression, and response to therapy of coronary atherosclerosis in a well-characterized cohort. We studied 375 subjects enrolled in the Lipoprotein and Coronary Atherosclerosis Study (LCAS). Genotypes were determined by polymerase chain reaction (PCR) and restriction mapping. Fasting plasma lipids and quantitative coronary angiograms were obtained at baseline and 2.5 years following randomization to fluvastatin or placebo. Distributions of genotypes were--for CD14: 100 CC, 184 CT, and 86 TT; IL-6: 152 GG, 153 GC, and 62 CC; and TNF-alpha: 244 GG, 110 GA, and 17 AA. The CD14 CC genotype was associated with incidence of new coronary occlusion (P=0.026); TNF-alpha AA genotype with history of myocardial infarction (MI, P=0.04), and A allele with total occlusions at baseline (P=0.027), and systolic blood pressure (P=0.046); and IL-6-174 CC genotype with baseline minimum lumen diameter (P=0.043) and reduction in lipoprotein(a) with fluvastatin (P=0.03). Otherwise, no association between the genotypes and the biochemical, angiographic, and clinical phenotypes was detected, and neither were genotype-treatment interactions. Functional variants of CD14 -260C/T, TNF-alpha -308G/A, and IL-6 -174G/C, implicated in the susceptibility to infection, are unlikely to confer major risk for susceptibility to coronary atherosclerosis and its progression or response to therapy in the LCAS population.     

Gene polymorphisms of TNF-α−308 (G/A), IL-10−1082 (G/A), IL-6−174 (G/C) and IL-1Ra (VNTR) in Egyptian cases with type 1 diabetes mellitus

Background. Type 1 diabetes (T1D) is a genetically conditioned autoimmune disease in which cytokines play an important role.

Objectives. To check for the association of polymorphisms of cytokine genes with type 1 diabetes.

Subjects. This work included 50 cases with T1D and 98 healthy individuals from the Nile Delta region of Egypt. Cases included 20 males and 30 females with a median age of 25 and range of 15–50 years.

Methods. DNA was amplified using PCR with sequence-specific primers for detection of polymorphisms related to tumor necrosis factor (TNF)-α^{? 308} (G/A), interleukin (IL)-10^{? 1082} (G/A), IL-6^{? 174} (G/C), and IL-1Ra (VNTR).

Results. Cases with T1D showed significant higher frequency of genotypes of TNF-α^{? 308} AA (p < 0.001, odds ratio (OR) = 7.91), IL-6-17CC (p < 0.05, OR = 3.36) and IL-1Ra A1A1 (p < 0.05, OR = 3.68) with significant lower frequencies of TNF-α^{? 308} GA, and IL-1Ra A1A2 genotypes (p < 0.001 and < 0.05, respectively). They also showed significant higher frequency of TNF-α^{? 308} allele A (p < 0.05, OR = 2.0), IL-1Ra allele A1 (p < 0.05, OR = 2.98) with a significant lower frequency of TNF-α^{? 308} G allele and IL-1Ra A2 allele (p < 0.05). No significant difference was detected among cases in relation to IL-10^{? 1082} (G/A) genotypes or alleles nor in relation to age, sex, consanguinity or family history of the disease.

Conclusions. Polymorphisms related to TNF-α and IL-1Ra genes may be considered genetic markers for T1D among Egyptians with a potential impact on family counseling and management.     

IL6 and FAS/FASL gene polymorphisms may be associated with disease progression in HIV-1-positive ethnically mixed patients

The progression of AIDS depends on the complex host and virus interactions. The most important disease progression hallmarks are immune activation and apoptosis. In this study, we address the prevalence of polymorphisms related to proinflammatory and apoptotic genes, such as IFNG (+874T/A), TNF (308G/A), IL6 (−174G/C), IL8 (−251A/T), FAS (−670A/G), and FASL (−124A/G) in 160 ethnically mixed HIV-1-infected patients from multicentre cohorts with different clinical outcomes (13 elite controllers [EC], 66 slow long-term non-progressors [LTNPs], and 81 progressors [P]). The genotyping was accomplished by TaqMan-qPCR. Among all the polymorphisms analyzed in the cytokines, the IL6 −174G/C polymorphism showed a higher frequency of GG genotype in the LTNP and LTNP+EC groups as compared to the P group. Moreover, there was a significantly higher frequency of the G allele in the LTNP and LTNP+EC groups as compared to the P group. On the other hand, the levels of CD4⁺ T lymphocytes were higher among individuals showing the AA and AG genotypes for the FASL −124A/G polymorphism as compared to the GG genotype. Furthermore, the AG and AA genotypes were more frequent, as compared to the GG genotype, in individuals showing a lower viral load. In contrast, for the FAS −670A/G polymorphism, a significantly higher viral load was observed in individuals with the AG genotype as compared to the GG genotype. In conclusion, we found three genetic allelic variants of the IL6 −174G/C, FASL −124A/G, and FAS −670A/G polymorphisms that were related to disease progression and immunological and virological markers in cohorts of HIV-1-positive ethnically mixed patients.     

Meta-Analysis of the Relationship between TNF-α (−308G/A) and IL-10 (−819C/T) Gene Polymorphisms and Susceptibility to Dengue

Objective: This study determined whether tumor necrosis factor alpha (TNF-α) and Interleukin-10 (IL-10) polymorphisms are associated with susceptibility to dengue.

Methods: a systematic review with meta-analysis was conducted of the associations between the TNF-α (?308G/A) and IL-10 (?819C/T) polymorphisms and dengue.

Results: A total of eight case-controls studies involving 384 individuals with symptomatic dengue, 571 individuals with dengue hemorrhagic fever, and 995 healthy controls were considered in the meta-analysis. There was no significant association between TNF-α (?308G/A) and IL-10 (?819C/T) polymorphism and dengue in overall population. However, stratifying meta-analysis by groups, the meta-analysis revealed association between the TNF-α ?308 G/G (OR: 1.62, CI: 1.02–2.57, p = 0.04) genotype and allele G (OR: 1.62, CI: 1.04–2.55, p = 0.03) that confers susceptibility to symptomatic dengue, while the TNF-α ?308 G/A genotype (OR: 0.69, CI = 0.39–0.99, p = 0.04) and allele A (OR: 0.64, CI: 0.41–1.00, p = 0.05) confers protection to symptomatic dengue. No difference was observed for the TNF-α (?308) and IL-10 (?819C/T) polymorphisms in the comparisons of hemorrhagic dengue versus control and hemorrhagic dengue versus symptomatic dengue.

Conclusion: This meta-analysis showed that TNF-α (?308) polymorphism is associated with dengue symptomatic susceptibility.     

Mental health and resiliency following 44 months of terrorism: a survey of an Israeli national representative sample

Background

Genetic variation in the innate immune system of the host may play a role in determining the risk of developing infection, as well as outcome from infection.

Methods

Infectious complications were retrospectively determined in 293 (233 African-American (AA), 57 Caucasian and 3 Hispanic) mechanically ventilated very low birth weight (VLBW) infants (<1500 grams at birth) who were genotyped for the IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T single nucleotide polymorphisms (SNPs).

Results

The IL-6 -174C allele was associated with an increased incidence of late blood stream infection (BSI) in AA but not Caucasian infants. In AA infants with the C allele the incidence of late BSI was 20/29 (69%) compared to 94/204 (46%) in homozygous GG infants (RR 2.6, 95% CI: 1.1–6.0, p = 0.021). The IL-10 -1082A allele was associated with an increased incidence of late BSI. One or more episodes of late BSI developed in 14 (35%) of 40 infants with the GG genotype, 71 (49%) of 145 infants with the GA genotype and 63 (58%) of 108 infants with the AA genotype (p = 0.036). Infants with the A allele (AA or GA genotypes) had an incidence of late BSI that was 134/253 (53%) compared to 14/40 (35%) in homozygous GG infants (RR 2.1, 95% CI: 1.04–4.19, p = 0.035). The CD14 -260 C/T SNP did not alter the overall risk for BSI in ventilated VLBW infants. Multiple BSI episodes were more common in the TT genotype group (CC: 17%, CT: 11%, TT: 30%, p = 0.022). This effect was due to the strong effect of the TT genotype on the incidence of multiple BSI in AA infants (CC: 15%, CT: 11%, TT: 39%, p = 0.003).

Conclusion

The IL-6 -174 G/C, IL-10 -1082 G/A and CD14 -260 C/T SNPs may alter risk for BSI in ventilated VLBW infants.     

IL-6 promoter polymorphism (?174G/C) and systemic lupus erythematosus

We investigated the possible association between susceptibility to systemic lupus erythematosus (SLE) and single-nucleotide polymorphisms located in the promoter region of the interleukin-6 gene (?174 G/C) in a sample of the Egyptian population and the contribution of this polymorphism in the clinical or immunological manifestation of the disease. Forty-two Egyptian patients with SLE and 40 unrelated healthy control volunteers were genotyped by polymerase chain reaction followed by visualization on 4% agarose gel electrophoresis on ultraviolet transilluminator to detect the genotype distribution and allelic frequencies of the polymorphisms. The homozygous GG genotypes was significantly increased in SLE patients compared to control group (p value?=?0.04). On the other hand, the heterozygous G/C genotype was significantly elevated in the controls compared to SLE patients (p value?=?0.01). The odds ratio value for G/G was 2.6 with a 95% CI from 1.1 to 6.7. As regard the association of clinical manifestations to the genotype frequency, we found a statistical significant increase in the frequency of GG genotype with chest disease, nephritis, and arthritis. From this study, we suggest that G carrier is more susceptible to develop SLE and that SNP may have a role in the pathogenesis of the disease and may be associated with some of its clinical manifestations.     

Sphingosine-1-phosphate acting via the S1P₁ receptor is a downstream signaling pathway in ceramide-induced hyperalgesia

Interleukin-6 (IL-6), identified as a pleiotropic inflammatory cytokine, plays important roles in the acute inflammatory response and in the modulation of the neuroimmune response. To date, large amounts of epidemiological studies have been performed to investigate the association between the IL-6 −174G/C polymorphism and Alzheimer's disease (AD) risk. Inconclusive results, however, have been reported. We aimed to assess the effect of the IL-6 −174G/C polymorphism on AD susceptibility with the use of a meta-analysis. 14 studies involving 3769 cases of AD and 9431 control subjects were identified by a search of Pubmed, Embase and ISI Web of Science databases. Crude odds ratios (ORs) with 95% confidence intervals (CIs) for the IL-6 −174G/C polymorphism and AD risk were computed using fixed- or random-effects model when appropriate. Obvious heterogeneity among studies was detected, and a borderline statistically significant association was observed between the IL-6 −174G/C polymorphism and AD risk in Caucasians (GG vs. CC: OR = 1.35, 95%CI, 1.06-1.72; GG/GC vs. CC: OR = 1.27, 95%CI, 1.05-1.53, respectively). After exclusion of one study, the heterogeneity disappeared and no significant association was observed between the polymorphism and AD risk. These findings indicate that the IL-6 −174G/C polymorphism may not be an independent risk factor for the development of AD.     

Interaction of polymorphisms in the genes encoding interleukin-6 and estrogen receptor beta on the susceptibility to Parkinson's disease.

The multifunctional cytokine interleukin-6 (IL-6) is involved in inflammatory processes in the central nervous system and increased levels of IL-6 have been found in patients with Parkinson's disease (PD). It is known that estrogen inhibits the production of IL-6, via action on estrogen receptors, thereby pointing to an important influence of estrogen on IL-6. In a previous study, we reported an association between a G/A single nucleotide polymorphism (SNP) at position 1730 in the gene coding for estrogen receptor beta (ERbeta) and age of onset of PD. To investigate the influence of a G/C SNP at position 174 in the promoter of the IL-6 gene, and the possible interaction of this SNP and the ERbeta G-1730A SNP on the risk for PD, the G-174C SNP was genotyped, by pyrosequencing, in 258 patients with PD and 308 controls. A significantly elevated frequency of the GG genotype of the IL-6 SNP was found in the patient group and this was most obvious among patients with an early age of onset (相似文献   

The IL6 -174G/C polymorphism and sudden infant death syndrome

The interleukin-6 genotype (IL6 -174GG) has been proposed to be associated with sudden infant death syndrome (SIDS). The aim of this study was to investigate the -174G/C polymorphism in 175 Norwegian SIDS cases and 71 controls. There were no differences in genotype distribution between these two groups (p = 1.0). This confirms the findings in a combined SIDS group compared with European Caucasian controls, but not findings in smaller cohorts of SIDS cases from Australia and England. The discrepancy may result from bias introduced when investigating only a few SIDS cases, differences in diagnostic criteria when diagnosing the cause of death as SIDS, and differences in the distribution of the -174G/C polymorphism in different ethnic groups. Findings of an activated immune system in SIDS indicate that genes involved in the immune response are of importance. However, because there are several polymorphisms in the IL6 gene promoter that could potentially regulate the expression of the gene, more than one polymorphism should be investigated to assess the involvement of the IL-6 gene in SIDS.     

Serum Leptin Levels,Leptin Receptor Gene (LEPR) Polymorphism,and the Risk of Systemic Lupus Erythematosus in Kashmiri Population

The study is conducted to evaluate relationship between LEPRQ223R (Gln?>?Arg) polymorphism, serum leptin levels, soluble leptin receptor (SOb-R) levels and SLE risk in Kashmiri population.LEPR genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method in 100 unrelated SLE patients and equal number of healthy control subjects. Leptin and SOb-R levels were measured by ELISA assays. The present study showed higher frequency of variant genotype (AG?+?GG) in cases compared to controls [OR?=?2.52, CI?=?1.18–5.35, p?=?0.03]. Moreover the rare (G) allele was significantly more predominant in cases than controls [OR?=?1.49, p?=?0.04]. Interestingly a positive association between the variant genotype and the development of arthritis [OR?=?11.8, CI?=?1.6–85.1, p?=?0.002] and an inverse association with cardiac disorder [OR?=?0.09, CI?=?0.02–0.46, p?=?0.001] was observed in this study. Furthermore the study showed significant differences of leptin levels in SLE patients and controls (23.9?±?19.5 vs 14.8?±?10.4, p?<?0.001). SLE patients in the highest quartile leptin levels (≥32.5?ng/mL) were significantly more likely to have higher BMI (p?=?0.001) and increased risk of developing arthritis (p?=?0.02). Furthermore positive association was observed between the variant genotype(AG?+?GG) and leptin levels (p?=?0.001) in SLE patients. Thus, it is evident from our study that LEPRQ223R polymorphism and elevated leptin levels are associated with increased susceptibility of SLE in Kashmiri population.