结直肠癌患者IL-6基因启动子-174G→C多态性研究

目的：观察结直肠癌患者是否存在IL-6基因启动子-174G→C位点的多态性。方法：采用PCR扩增、限制性内切酶片段长度多态性（RFLP）分析判断46例结直肠患者IL-6启动子-174G→C多态性。结果：全组结直肠癌患者IL-6基因启动子-174位点均为GG型。结论：本组结直肠癌患者中未发现IL-6基因启动子-174位点的多态性。     

Interleukin-6 gene polymorphism and insulin sensitivity

Type 2 diabetes and the insulin resistance syndrome have been hypothesized to constitute manifestations of an ongoing acute-phase response. We aimed to study an interleukin-6 (IL-6) gene polymorphism in relation to insulin sensitivity (IL-6 is the main cytokine involved in an acute-phase response). Subjects homozygous for the C allele at position -174 of the IL-6 gene (SfaNI genotype), associated to lower plasma IL-6 levels, showed significantly lower integrated area under the curve of serum glucose concentrations (AUCglucose) after an oral glucose tolerance test, lower blood glycosylated hemoglobin, lower fasting insulin levels, lower total and differential white blood cell count (a putative marker of peripheral IL-6 action), and an increased insulin sensitivity index than carriers of the G allele, despite similar age and body composition. A gene dosage effect was especially remarkable for AUCglucose (6.4 vs. 9.3 vs. 9.7 mmol/l in C/C, C/G, and G/G individuals, respectively). The serum concentration of fully glycosylated cortisol binding globulin (another marker of IL-6 action), suggested by concanavalin A adsorption, was lower in C/C subjects than in G/G individuals (32.6+/-2.9 vs. 37.6+/-4.6 mg/l, P = 0.03). In summary, a polymorphism of the IL-6 gene influences the relationship among insulin sensitivity, postload glucose levels, and peripheral white blood cell count.     

IL-6 promoter polymorphism -174 is associated with new-onset diabetes after transplantation

New-onset diabetes after transplantation (NODAT) is a serious complication of transplantation. This study tested whether IL-6 production capacity may influence the development of NODAT in two different groups of patients. The occurrence of NODAT was analyzed with respect to IL-6 gene promoter polymorphism at position -174 (G-->C) and other relevant risk factors retrospectively in 217 renal transplant recipients and prospectively in 132. A linear increase in both circulating IL-6 (P = 0.09) and C-reactive protein (an indicator of basal IL-6 secretion; P = 0.03) concentrations from the CC genotype to the GG genotype was observed. In the multivariate model, the CC genotype was associated with a decreased risk for NODAT compared with the GG genotype in the two cohorts. Homeostasis Model Assessment for Insulin Resistance also revealed lesser insulin sensitivity in the GG carriers than in the CC carriers (2.15 +/- 2 versus 1.32 +/- 1.03; P = 0.03). Subgroup analysis showed that the influence of IL-6 gene promoter polymorphism on the development of NODAT was restricted mostly to overweight patients. These results highly suggest that IL-6 production capacity influences the development of NODAT and that diabetes-inducing drug administration should be limited in overweight patients who carry the GG genotype.     

P-选择素基因多态性与急性胰腺炎相关性分析

目的 ：探讨P-选择素（P-s electin）基因启动子区C-2123G多态性与急性胰腺炎（acute pan-creatitis,AP）发展及预后的相关性。方法：应用聚合酶链反应-限制性片段长度多态性（PCR-RELP）的分析方法,检测102例健康志愿者和119例AP患者P-selectin基因启动子区C-2123G的基因多态性,计算其基因型频率及等位基因频率。结果：健康对照组与AP组C-2123G等位基因频率（C32.35%,G 67.65%）及基因型分布（C纯合子占19.33%,CG占26.05%,G纯合子占54.62%）一致。轻症急性胰腺炎（MAP）组和重症急性胰腺炎（SAP）组等位基因频率及基因型分布差别无统计学意义。发生重症脓毒症患者G等位基因频率（83.33%）高于非脓毒症组（56.76%,P〈0.05）,GG纯合子患者发生重症脓毒症比例高于非脓毒症组（P〈0.05）。结论：P-selectin C-2123G基因多态性在AP发生重症脓毒症中具有重要的作用,是AP病情进展的危险因素。     

The interleukin-6 -174promoter polymorphism is associated with long-term kidney allograft survival

BACKGROUND: Th1-dependent effector mechanisms may be responsible for allograft rejection. Recently, interleukin-6 (IL-6) has been shown to antagonize CD4+ T cells to effector Th2 cells and, in the process, differentiate them into Th1 cells. METHODS: To assess the role of IL-6 in long-term allograft survival, 158 patients after first cadaveric kidney transplantation were analyzed for the biallelic -174G-->C promoter polymorphism of the IL-6 gene. RESULTS: Carriers of the -174C-allele (genotype GC/CC) had an inferior three-year graft survival (71/104 = 68.3%; P = 0.0059) with a 3.7-fold increased relative risk of graft loss compared to carriers of the -174GG-genotype (48/54 = 88.9%). The -174GC/CC-genotype retained its negative impact on graft survival when other established prognostic factors and further cytokine polymorphisms (-308TNF-alpha, TGF-beta1 codon 10 & 25, -592/-819/-1082IL-10 and +874IFN-gamma) were considered simultaneously. CONCLUSIONS: Since the clinical impact on transplant outcome seems as important as matching for histocompatibility antigens, genotyping of the IL-6 -174polymorphism may offer a new method for identifying patients at increased risk of allograft loss.     

Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis

Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease.     

Association of interleukin-6 -174G/C promoter polymorphism with hypertension and left ventricular hypertrophy in dialysis patients

BACKGROUND: Gene polymorphisms of proinflammatory cytokines, such as interleukin-6 (IL-6) and the chemokine receptor CX3CR1, have been found in association with cardiovascular disease in the general population. In dialysis patients, in whom the prevalence of cardiovascular comorbidity is strikingly high, these polymorphisms have not been investigated. METHODS: The -174G/C polymorphism of the IL-6 gene and the chemokine receptor CX3CR1 polymorphisms 249V/I and 280T/M were examined for their association with cardiovascular abnormalities in a cohort of 161 patients with end-stage renal disease (ESRD) treated by hemodialysis. Arterial blood pressure, electrocardiogram (ECG) ischemic changes, and left ventricular mass index (LVMI) were the parameters examined for the association study. The control group was made up of 169 healthy subjects. RESULTS: We found that for both IL-6 and chemokine receptor, genotype frequency and allelic distribution in both ESRD patients and controls were comparable. The genetic association study showed that in the whole group of dialysis patients, individuals with GC + CC genotype for the -174G/C polymorphism had a higher diastolic blood pressure (P = 0.008) and LVMI (P = 0.026) than GG homozygotes. The prevalence of left ventricular hypertrophy (LVH) in the former group was 58.6% vs. 39.2% in the latter (P = 0.02). The same analysis limited to diabetic patients in dialysis, showed that the prevalence of LVH in those with CG + CC genotype was 87.5% vs. 36.3% in those with GG genotype (P = 0.02). In diabetic patients, lower levels of serum albumin was found in the GC + CC genotypic group than in GG subjects; 34.63 +/- 5.18 g/L vs. 41.75 +/- 4.79 g/L (P = 0.003). CONCLUSION: These data demonstrate an association between the IL-6 promoter polymorphism -174G/C and high blood pressure and LVH in hemodialysis patients, especially those with diabetes. The results strengthen the hypothesis that chronic inflammation is a mechanism of cardiovascular damage in dialysis patients and the role played by the IL-6 system in this mechanism.     

Association of IL-6 G-174C polymorphism with bone mineral density

Functional polymorphisms in the promoter region of interleukin-6 (IL-6) are known to be involved in bone mineral density (BMD) and the development of osteoporosis, but the reported results have been inconsistent. Using the meta-analysis approach, the present study is designed to provide a relatively comprehensive picture of the relationship between bone mineral density (BMD) or osteoporosis and polymorphisms in the promoter region of IL-6 (rs1800795 and rs1800796). The difference of bone mineral density (BMD) values between genotypes was examined by mean difference and 95 % confidence intervals (CIs). Association between IL-6 polymorphism and clinical osteoporosis was evaluated by pooled odds ratios (ORs) and 95 % CIs. A total of 13 articles with 11,499 subjects were included in the present study. For ?174 (rs1800795), we found that individuals with the G/G genotype had a significantly lower BMD value than those with C/C genotype at femoral neck (0.02 g/cm², 95 % CI 0.00–0.03) (p = 0.04) and distal radius (0.01 g/cm², 95 %CI 0.01–0.01) (p < 0.0001). However, we did not find a statistically significant difference of BMD at the spine. When analysis was limited to postmenopausal women, similar results were obtained. We further found that the C/C genotype was associated with a reduced risk of osteoporosis compared to G/G genotype, and the pooled OR was 0.72 (95 % CI 0.54–0.95, p = 0.02). In addition, a significant relationship was found between G-634C (rs1800796) polymorphism and distal radius BMD (CC vs. GG: 0.02 g/cm², 95 % CI 0.01–0.03; GC vs. GG: 0.02 g/cm², 95 % CI 0.00–0.03) in the Asian population. These findings suggest that the CC genotype of IL-6 G-174C polymorphism may be associated with high BMD at femoral neck and distal radius and decreased risk of osteoporosis in the Caucasian population whereas G-634C polymorphism was associated with distal radius BMD in Asians.     

Effect of IL-6 C-572G polymorphism on idiopathic membranous nephropathy risk in a Han Chinese population

Membranous glomerulonephritis (MGN) is viewed as an immune-mediated glomerular disease, with immunologic expression occurring in genetically susceptible persons. The cytokine interleukin-6 (IL-6) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune response. Our study gauged the effects of IL-6 C-572G (rs1800796) single nucleotide polymorphism (SNP) on MGN among Taiwan's Han Chinese population, as analyzed in 265 controls and 106 MGN patients. Genotyping for IL-6 C-572G SNP was performed by restriction fragment length polymorphism assay. Data showed stark differences in genotype and allele frequency distributions at IL-6 C-572G SNP between MGN patients and controls (p = 1.6E-04 and 1.7E-04, respectively). People with C allele or with CC genotype at IL-6 C-572G SNP showed higher risk of MGN (odds ratio = 2.42 and 2.71, respectively; 95% confidence interval = 1.51-3.87 and 1.60-4.60, respectively). These point to IL-6 C-572G polymorphism as the underlying cause of MGN; polymorphism merits further investigation.     

Effect of IL-6 C-572G polymorphism on idiopathic membranous nephropathy risk in a han chinese population

Membranous glomerulonephritis (MGN) is viewed as an immune-mediated glomerular disease, with immunologic expression occurring in genetically susceptible persons. The cytokine interleukin-6 (IL-6) gene polymorphism is known to impair intracellular signaling pathways following adaptive immune response. Our study gauged the effects of IL-6 C-572G (rs1800796) single nucleotide polymorphism (SNP) on MGN among Taiwan's Han Chinese population, as analyzed in 265 controls and 106 MGN patients. Genotyping for IL-6 C-572G SNP was performed by restriction fragment length polymorphism assay. Data showed stark differences in genotype and allele frequency distributions at IL-6 C-572G SNP between MGN patients and controls (p = 1.6E-04 and 1.7E-04, respectively). People with C allele or with CC genotype at IL-6 C-572G SNP showed higher risk of MGN (odds ratio = 2.42 and 2.71, respectively; 95% confidence interval = 1.51–3.87 and 1.60–4.60, respectively). These point to IL-6 C-572G polymorphism as the underlying cause of MGN; polymorphism merits further investigation.     

Association between IL-6 -174G/C polymorphism and acute rejection of renal allograft: evidence from a meta-analysis

Background

Results from published studies on the association of donor or recipient IL-6 -174G/C (rs1800795) polymorphism with acute rejection (AR) of renal allograft are conflicting. We performed a meta-analysis to estimate the possible association.

Methods

Studies were identified by searching PUBMED and EMBASE until July 1, 2011. Meta-analysis was performed in a fixed/random effects model using Revman 5.0.25 and STATA10.0.

Results

Seven studies addressing the association between donor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism and acute rejection of renal allograft were identified. Pooled OR based on 341 cases (whose recipient developed acute rejection) and 702 controls (whose recipient did not develop acute rejection) was 0.59 (95% CI, 0.26-1.33; p = 0.20), with a strong between-study heterogeneity. No association was observed in the subgroup analysis based on ethnicity. 13 studies evaluating the association between recipient IL-6 -174G/C polymorphism and acute rejection were identified. Pooled OR based on 451 cases (patients did not develop acute rejection) and 848 controls was 1.00 (95% CI = 0.72-1.37; p = 0.98), with a weak between-study heterogeneity.

Conclusions

Donor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism had a tendency of decreased risk for acute rejection, although it was not statistically significant. Recipient high producer genotype was not associated with acute rejection of renal allograft. Additional well designed studies with larger sample size are needed to support our findings, especially for the association between donor high producer genotype (G/G and G/C) of IL-6 -174G/C polymorphism and acute renal allograft rejection.     

Influence of interleukin-6 promoter polymorphism -174 g/c on kidney graft outcome

Background

The cytokine interleukin-6 (IL-6) is important in both immune responses and cardiovascular diseases. The IL-6 promoter polymorphism −174 G/C is associated with increased plasma concentrations of IL-6. The relationship between IL-6 polymorphisms and graft survival, cardiovascular events, and new-onset diabetes mellitus after kidney transplantation is controversial.

Objective

To analyze whether IL-6 (−174 G/C) polymorphism influences kidney graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.

Methods

The IL-6 promoter polymorphism (−174 G/C) was analyzed using the polymerase chain reaction with sequence-specific primers in 335 kidney transplant recipients. Data for graft survival, chronic graft nephropathy, cardiovascular events, and new-onset diabetes were obtained retrospectively from clinical records. Categorical variables were compared between individuals with CC, GG, and GC genotypes using χ² tests. Survival analysis was performed using the Kaplan-Meier method, comparing groups using the log-rank test.

Results

No significant differences were observed in 5-year graft survival between individuals with CC and GC/GG genotypes (85.3% vs 77.1%; P = .22). Nor were significant differences noted in the rates of chronic allograft nephropathy (37.5% vs 33.8%; P = .48), cardiovascular events (10.0% vs 23.0%; P = .10), or new-onset diabetes (7.5% vs 11.8%; P = .28).

Conclusion

There is no association between IL-6 (−174 G/C) polymorphism and graft survival or development of chronic allograft nephropathy, cardiovascular events, or new- onset diabetes.     

A meta-analysis on correlation between interleukin-6 -174G/C polymorphism and end-stage renal disease

Background: The level of interleukin-6 (IL-6) and its gene polymorphism are associated with the end-stage renal disease (ESRD) and the related complications. This study aimed to investigate the correction between IL-6 -174G/C polymorphism and ESRD by meta-analysis.

Methods: Using the databases including PubMed, Embase, Cochrane library, CNKI, and CBM, the data of case-control studies on correlation between IL-6 -174G/C polymorphism and ESRD from database establishment to January 2016 were collected. According to inclusion and exclusion criteria, the quality of literatures was evaluated. The relevant research data were extracted, followed by meta-analysis using Revman 5.3 software (London, UK). The combined odds ratio (OR) and 95% confidence interval (95%CI) of each genetic model were calculated, and the publication bias data was assessed using the Stata 12.0 software (College Station, TX).

Results: A total of five literatures were included, with 1199 cases in case group and 1089 cases in control group. Meta-analysis showed that, there was no significant correlation between each genetic model of IL-6 -174G/C polymorphism and ESRD [(C versus G): OR?=?1.36, 95%CI (0.69, 2.66), p?=?.38; (CC?+?GC versus GG): OR?=?1.28, 95%CI (0.58, 2.82), p?=?.54; (CC versus GG?+?GC): OR?=?1.71, 95%CI (0.82, 3.54), p?=?.15; (CC versus GG): OR?=?1.74, 95%CI (0.76, 3.99), p?=?.19; (GC versus GG): OR?=?1.18, 95%CI (0.55, 2.54), p?=?.67]. The race subgroup analysis showed that, there was no significant correlation between each genetic model of IL-6 -174G/C polymorphism and ESRD in the Caucasians (p?>?.05).

Conclusion: IL-6 -174G/C polymorphism has no significant correlation with the susceptibility risk of ESRD, and may not be a risk factor for ESRD.     

醛固酮瘤CYP11B2基因C-344T位点单核苷酸多态性与其发病关系

目的探讨醛固酮瘤CYP11B2基因启动子区C-344T位点单核苷酸多态性与醛固酮瘤患者发病之间的关系。方法应用RT-PCR检测醛固酮瘤（醛固酮瘤肿瘤组织标本34例,醛固酮瘤肿瘤病理切片标本44例）和正常肾上腺组织（13例）中SF-1基因的mRNA表达水平,PCR-RFLP技术检测醛固酮瘤CYP11B2基因C-344T位点基因型。结果在醛固酮瘤中SF-1基因的表达与正常肾上腺组织的无明显差别（P=0.919）,醛固酮瘤病例中CYP11B2基因启动子区C-344T位点C等位点频率明显高于正常人,差异有统计学意义（χ2=6.876,P=0.009）。结论醛固酮瘤CYP11B2基因启动区C-344T位点中C等位点与类固醇合成因子结合率高于T等位点,C等位点与醛固酮瘤患者高醛固酮血症有关。