白细胞介素6受体基因多态性与代谢综合征的相关性研究

探讨白细胞介素6受体(IL-6R)基因启动子- 183A/G(rs4845617)和外显子9Asp358Ala( rs8192284 A/C)多态性与代谢综合征(MS)的相关性.结果显示IL-6R基因rs8192284A/C多态性在MS组AA基因型频率和A等位基因频率高于正常对照组(P＜0.05或P＜0.01),携带A等位基因的患者发生MS的风险是C等位基因的1.643倍(95％CI 1.163 ～2.320,P＜0.01);而-183A/G三种基因型频率和等位基因频率差异无统计学意义(P＞0.05).提示IL-6R基因Asp358Ala多态可能与中国国人MS相关.     

Fetuin‐A and interleukin‐18 levels in ankylosing spondylitis

Aim: Interleukin‐18 (IL‐18) and fetuin‐A have been implicated in atherosclerosis. Preliminary evidence suggests that ankylosing spondylitis (AS) is associated with an increased risk of atherosclerosis. The aim of the present study was to investigate possible abnormalities in IL‐18 and fetuin‐A levels in AS. Methods: Subjects without established cardiovascular (CV) risk factors were studied. Fasting glucose, serum lipids, high sensitive C‐reactive protein (hsCRP), erythrocyte sedimentation rate, IL‐18 and fetuin‐A were assessed. Patients were also evaluated with the Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index, and the Bath Ankylosing Spondylitis Disease Activity Index. Results: Fourty‐five patients with AS (37.4 ± 9.7 years; 35M/10F) and 29 controls (35.5 ± 11.1 years; 21M/8F) were studied. Fetuin‐A levels were significantly higher in AS patients compared to controls (1023.5 ± 171.6 vs. 856.9 ± 207.9 μg/mL, P < 0.001). IL‐18 levels were also higher in the AS group but the difference was not significant (184 ± 186 vs. 140 ± 115, P = 0.1). Significant but weak correlations were found between fetuin‐A, IL‐18, hsCRP, low density lipoprotein cholesterol, and triglyceride levels (P < 0.05; r = 0.4, 0.3, 0.2, and 0.3 respectively). Comparison of subjects with respect to the treatment type, disease activity and history of peripheral arthritis yielded no difference regarding fetuin‐A and IL‐18 between groups. Conclusion: Fetuin‐A and IL‐18 levels seem to be increased in AS patients regardless of disease activity and treatment type.     

Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus

<正>Objective To investigate the relationships between glucokinase(GCK)gene 6(tag single-nucleotide polymorphisms,tag SNPs)sites which named rs12702070,rs2971672,rs2268569,rs2268573,rs2300587 and rs1476891 polymorphisms and type 2 diabetes in Chinese Southern Han Population.Methods This study was designed as a case-control.499 type 2 diabetes patients     

A biologically important single nucleotide polymorphism within the toll-like receptor-4 gene is not associated with rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis (RA) is a heterogeneous condition affecting 1-2% of the population. Genetics account for 30% of disease susceptibility, with one third arising from the Major Histocompatibility Complex. The toll-like receptor 4 (TLR-4) gene which has been mapped to chromosome 9 (9q32-q33) is involved in innate immune recognition with subsequent proinflammatory cytokine release including TNF. A single nucleotide polymorphism (+896A-->G) resulting in the amino acid substitution (Asp299Gly) has been shown to interrupt TLR-4 mediated signalling. OBJECTIVE: We sought to determine if this TLR-4 polymorphism influences susceptibility to rheumatoid arthritis. METHODS: DNA was extracted from 879 healthy controls and 212 rheumatoid arthritis patients recruited from the north of England. Genotyping was performed using a 5' nuclease Taqman allelic discrimination assay. Allele frequencies were compared between the two groups. We also examined whether an association existed in non-carriers of the DRB1 shared epitope alleles. RESULTS: The frequency of the rare allele was 5.9% in the controls and 7% in the patients. Comparison of rare allele carriage between controls and patients revealed no significant difference p = 0.13. This was also the case in shared epitope negative individuals p = 0.92. CONCLUSION: The TLR-4 +896 polymorphism does not appear to influence susceptibility to rheumatoid arthritis.     

Association of interleukin‐6 and interleukin‐10 genotypes with radiographic damage in rheumatoid arthritis is dependent on autoantibody status

Objective

Recent evidence has highlighted a major genetic contribution to radiographic damage in rheumatoid arthritis (RA). The objective of this study was to determine whether genetic variants in the loci for interleukin‐1 (IL‐1), IL‐6, IL‐10, protein tyrosine phosphatase N22 (PTPN22), and selenoprotein S are associated with radiographic damage.

Methods

Modified Larsen scores of radiographic damage were determined in a cross‐sectional population of patients with RA (n = 964). Rheumatoid factor (RF) and anti–cyclic citrullinated peptide (anti‐CCP) were also assayed. The Kruskal‐Wallis nonparametric test was used to compare median radiographic damage scores across genotype groups, followed by the Cuzick nonparametric test for trend to assess gene‐dose effects.

Results

An allele‐dose association of IL‐6 −174G with increasing radiographic damage was present (P = 0.005), but only in patients who were RF positive (P = 0.004) or anti‐CCP positive (P = 0.01). Patients with the IL‐10 −592CC genotype had more extensive radiographic damage than did those with the AC or AA genotype (P = 0.006), but this was observed only among patients who were RF negative (P = 0.002) or anti‐CCP negative (P = 0.002). However, RF status and anti‐CCP status were not associated with the IL‐6 or IL‐10 genotype. No other genetic associations were detected, apart from a marginal association of PTPN22 +1858T with increased radiographic damage.

Conclusion

The reported associations of IL‐6 −174G with high IL‐6 production and IL‐10 −592 with low IL‐10 production and our own results support a role of genetically determined dysregulated cytokine production in disease severity. The lack of association of these genotypes with RF and anti‐CCP antibody status suggests that they act downstream of autoantibody production. We conclude that IL‐6 and IL‐10 genotypes may be useful in predicting disease severity in autoantibody‐positive and autoantibody‐negative patients, respectively.

     

IFABP基因单核苷酸多态性与2型糖尿病患者血清脂质水平的关系

目的 探讨2型糖尿病(T2DM)患者小肠脂肪酸结合蛋白(IFABP)基因54A/T单核苷酸多态性(SNP)对血清脂质水平的影响.方法 T2DM患者136例,正常对照组112例.利用PCR、HhaI内切酶酶切、基因测序等技术检测各组IFABP基因型;血清脂质指标的检测采用生物化学方法.结果 与对照组比较,T2DM组54T等位基因分布频率无统计学差异(χ2=0.23,P＞0.05).在T2DM组,与54A等位基因携带者比较,54T等位基因携带者血清TG明显升高(1.52±0.67 vs 1.29±0.48 mmol/L,P＜0.05),HDL-C、Apo-A1虽有降低,但差异无统计学意义(1.09±0.20 vs 1.17±0.30 mmol/L,P＞0.05;1.56±0.13 vs 1.60±0.15 g/L,P＞0.05).结论 IFABP基因A54T突变可能是促进T2DM患者心血管病变进程的一个潜在因素.     

P-选择素基因单核苷酸多态性与IgA肾病的相关性

目的研究P-选择素基因变异与原发性IgA肾病的相关性。方法在用直接测序法广泛筛查P-选择素基因全部编码区、部分调控区和外显子-内含子连接区并发现16个单核苷酸多态性(SNP)的基础上,挑选9个中高频SNPs(频率>5％)。选上海瑞金医院肾科收治的汉族原发性IgA肾病患者210例及健康对照者103例,用PCR产物直接测序法进行基因分型,对IgA肾病进行病例-对照相关分析。结果(1)IgA肾病者AA基因型频率(78．1％)明显高于健康对照者(65．1％,P =0．0136),AG+GG基因型频率(21．9％)明显低于健康对照者(34．9％,P=0．0136);IgA肾病者等位基因A频率(88．6％)明显高于健康对照者(81．6％,P=0．0165),等位基因G频率(11．4％)明显低于健康对照者(18．4％,P=0．0165)。危险度相关分析,AG+GG基因型使IgA肾病发病危险性下降为52．2％(OR=0．522,95％CI为0．311～0．875)。(2)96例IgA肾病者外周血P-选择素水平为(26．8±9．1)μg／L,显著高于健康对照者[(19．6±4．5)μg／L,P<0．01],-825A／G多态性AA基因型者的P-选择素水平[(28．1±9．0)μg／L]显著高于AG+GG基因型[(23．4±8．5)μg／L,P<0．05]。结论P-选择素基因启动子区-825A／G与IgA肾病易感性及患者肾功能显著相关,揭示了P-选择素基因在IgA肾病中的致病作用。     

EGFR基因单核苷酸多态性与结直肠癌的相关性

目的 探讨表皮生长因子受体(EGFR)基因第13外显子G64A单核苷酸多态性与结直肠癌的相关性.方法 应用PCR-RFLP法结合DNA测序法对49例结直肠癌患者外周血DNA中EGFR基因的第13外显子G64A单核苷酸多态性位点的等位基因进行检测.分析G/G、G/A、A/A基因型的分布及与结直肠癌患者临床病理特征的关系.结果 EGFR基因第13外显子G64A多态性位点G/G、G/A、A/A基因型频率分别为26.5%、59.2%、14.3%,与患者的性别、年龄、肿瘤生长部位、体积、浸润深度、大体形态、组织学类型、分化程度、血道转移无相关性(P＞0.05),与淋巴结转移和TNM分期相关(P＜0.05),携带G/A、G/G基因型和G等位基因的结直肠癌患者淋巴结转移风险增加(基因型G/G、G/A与A/A比较的OR分别为7.0、1.3,等位基因G与A比较的OR为2.7)、TNM分期递增(基因型A/A、G/A、G/G的平均秩次分别为18.43、23.14、32.69,等位基因A与G的平均秩次分别为42.71、54.81).结论 检测EGFR基因第13外显子G64A单核苷酸多态性有助于评估结直肠癌患者淋巴结转移情况和预后.     

A single nucleotide polymorphism within Ninjurin 2 is associated with risk of multiple sclerosis

Metabolic Brain Disease - Multiple sclerosis (MS) is a devastating inflammatory disease of the central nervous system (CNS) associated with loss of myelin sheaths. The role of Schwan cells in the...     

Elevated plasma activator inhibitor 1 is not related to insulin resistance and to gene polymorphism in healthy centenarians

Previous studies demonstrated a relationship between the degree of insulin resistance and plasma plasminogen activator inhibitor type-1 (PAI-1) levels. We aim at investigating the relationship between the degree of insulin resistance and plasma PAI-1 levels in aged subjects (n=83) and in healthy centenarians (n=42). In all subjects the degree of insulin resistance was assessed by HOMA method. Our data demonstrated that healthy centenarians have higher plasma PAI-1 levels (73.1±13.9 vs 23.7±14.7 ng/ml, P<0.001) and lower degree of insulin resistance (1.4±0.5 vs 3.3±1.3, P<0.001) than aged subjects. In aged subjects plasma PAI-1 levels correlated with the degree of insulin resistance (r=0.61, P<0.001), fasting plasma triglycerides (r=0.74, P<0.001) and age (r=0.33, P<0.001). All such associations were lost in centenarians. Plasma PAI-1 Ag levels were also similar in aged subjects and centenarians even after categorization for PAI gene polymorphism. In multivariate analysis, a model made by age, sex, body mass index, fasting plasma triglycerides, HOMA and PAI-1 gene explained 65 and 50% of plasma PAI-1 level variations in aged subjects and centenarians, respectively. Nevertheless, HOMA (P<0.001) was significantly and independently associated with plasma PAI-1 levels only in aged subjects. In conclusion, our data demonstrates that in healthy centenarians, plasma PAI-1 were not associated with the degree of insulin resistance as in aged subjects. Frequency of PAI-1 genotype does not provide an explanation for such differences between aged subjects and centenarians.