Analysis of EGF+61A>G polymorphism and EGF serum levels in Brazilian glioma patients treated with perillyl alcohol-based therapy

Purpose

Malignant gliomas are associated with alteration in EGF/EGFR signaling. Functional EGF+61A>G polymorphism is implicated with risk, recurrence, and progression of glioma. This study aimed to establish a putative association of EGF+61A>G with risk of glioma development, production of angiogenic growth factor EGF, and the response to perillyl alcohol administered by intranasal route.

Methods

The study included 83 patients with recurrent glioma enrolled in Phase I/II trial for intranasal perillyl alcohol therapy and subjects without cancer (n?=?196) as control group. DNA was extracted from blood samples, EGF genotype performed with PCR–RFLP assay, and EGF circulating levels by enzyme immunoassay. Adequate statistical tests were performed to verify associations between polymorphism and glioma risk, and genotype correlation with EGF circulating levels. The log-rank test was also used to evaluate differences on patient survival.

Results

Patients with primary glioblastoma had high frequency of AA genotype (p?=?0.037) and A allele (p?=?0.037). Increased EGF circulating levels were observed in glioma patients with AA (p?=?0.042), AG (p?=?0.006), and AA?+?AG (p?=?0.008) genotypes compared with GG. Patients with GG genotype showed increased but not significant (p?>?0.05) survival rate, and EGF levels lower than 250?pg/mL was consistently (p?=?0.0374) associated with increased survival.

Conclusion

Presence of EGF+61A>G polymorphism in Brazilian subjects was associated with glioma risk and increased circulating EGF levels. Better response to perillyl alcohol-based therapy was observed in a group of adult Brazilian subjects with lower EGF levels.     

Impact of interleukin 6 promoter polymorphisms (−174 G > C, −572 G > C and −597 G > A) on plasma IL-6 levels and their influence on the development of DVT: a study from India

ABSTRACT

Objectives: To evaluate the association of interleukin 6 (IL-6) levels with deep vein thrombosis (DVT) and to assess the impact of IL-6 promoter polymorphisms (?174G?>?C, ?572G?>?C and ?597G?>?A) on its plasma levels and their influence in the development of DVT in India.

Methods: One hundred DVT patients and 100 age and sex-matched healthy controls were study subjects. IL-6 polymorphisms were identified by polymerase chain reaction-restriction fragment length polymorphism. IL-6 levels were detected by enzyme-linked immunosorbent assay.

Results: Significantly raised IL-6 levels were observed in patients as compared to controls. (Patients: 13.73?±?6.30?pg/ml, Controls: 11.83?±?4.47?pg/ml, p?=?0.014). The prevalence of C allele of ?572G?>?C polymorphism was significantly higher in patients than controls (Patients: 39.5%, Controls: 27.5%, p?=?0.011, χ²=6.463). Subjects with GC and CC genotype had significantly higher IL-6 levels than GG genotype (p=<0.001). Patients with GC and CC genotype increased the DVT risk by 1.39 fold (OR^a: 1.39, CI: 0.74–2.62) and 2.69 fold (OR^a: 2.42, CI: 1.08–6.70), respectively. IL-6 ?174G?>?C and ?597G?>?A polymorphisms were not associated with raised IL-6 levels and nor with thrombotic risk (?174G?>?C: p?=?0.823 χ²=0.369; ?597G?>?A: p?=?0.678 χ²=1.08).

Conclusion: Our study emphasizes the importance of ?572G?>?C polymorphism in increasing IL-6 levels, thereby showing its significant role in DVT in India. IL-6 ?174G?>?C and ?597G?>?A were neither associated with raised plasma IL-6 levels nor with thrombotic risk. Thus ?572G?>?C polymorphism detection may be one of the connecting links between IL-6 and thrombotic risk in Indian DVT patients.     

+61A>G polymorphism in the EGF gene does not increase the risk of lung cancer

BACKGROUND AND OBJECTIVES: Epidermal growth factor (EGF) plays an important role in tumourigenesis by binding with its receptor, EGFR. Variations in the DNA sequence in the EGF gene can lead to an alteration in EGF production and/or activity, which can affect an individual's susceptibility to lung cancer. To test this hypothesis, this study examined the association between the +61 A>G polymorphism in the 5'-untranslated region of the EGF gene and the risk of lung cancer in a Korean population. METHODS: The EGF+61 A>G genotype was determined in 432 lung cancer patients and 432 healthy age- and gender-matched control subjects. RESults: The +61 AA and +61 AG genotypes were not significantly associated with the risk of lung cancer compared with the +61 GG genotype (adjusted OR = 1.02, 95% CI: 0.77-1.37; and adjusted OR = 0.81, 95% CI: 0.51-1.29, respectively). In addition to the reference model, the EGF+61 A>G polymorphism had no significant association with the risk of lung cancer under both dominant and recessive models for the +61A allele (adjusted OR = 0.98, 95% CI: 0.74-1.29; and adjusted OR = 0.80, 95% CI: 0.51-1.24, respectively). CONCLUSION: These results suggest that the EGF+61 A>G polymorphism may not significantly affect the susceptibility to lung cancer in the Korean population.     

CD209-336A/G promotor polymorphism and its clinical associations in sickle cell disease Egyptian Pediatric patients

Objectives

To detect the frequency of CD209 A>G polymorphism in sickle cell disease (SCD) Egyptian patients and to evaluate the use of CD209 A>G polymorphism as a genetic predictor of SCD clinical heterogeneity.

The single-nucleotide polymorphism (SNP) of tumor necrosis factor α −308G/A gene is associated with early-onset primary knee osteoarthritis in an Egyptian female population

The objective of the present study is to investigate if there is a potential association between the single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor alpha gene (TNF-α ?308G/A, rs1800629) and the susceptibility to and severity of early-onset knee osteoarthritis in the Egyptian female population. Genotype distributions and allelic frequencies of TNF-α ?308G/A polymorphism were investigated in 210 knee osteoarthritis (OA) patients and 210 age-, sex-, and ethnicity-matched healthy controls (HC). Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) amplifications were implemented to determine TNF-α ?308G/A SNP. Serum and synovial fluid levels of TNF-α, besides ESR and CRP, as laboratory markers for inflammation, were estimated for all patients and HC. Plain X-ray as well as MRI knee was done for grading of OA. Disease severity was estimated by Western Ontario and McMaster University Osteoarthritis scores. Percentages of TNF-α-G308A genotypes GG, AG, and AA were 85.7, 11.9, and 2.4% in OA patients and 54.7, 39.1, and 6.2% in controls, respectively. The frequencies of the GG genotype and G allele were significantly higher in subjects with knee OA than in HC (P = 0.04 and P < 0.001, respectively). Logistic regression analysis showed that the GG genotype and G allele are independently associated with increased risk for knee OA (odds ratio = 3.13, 95% confidence interval = 1.04–9.39, P = 0.04 for GG genotype, and odds ratio = 3.81, 95% confidence interval = 2.52–5.76, P = 0.001 for G allele). There is a close relationship between TNF-α-G308A polymorphism and individual susceptibility to and severity of early-onset knee OA in the Egyptian females.     

中国北方汉族IgA肾病患者UG基因G38A基因多态性与临床和预后的关系

目的　探讨中国北方汉族IgA肾病患者UG基因G3 8A基因多态性的分布及与临床和预后的关系。方法　选 3 0 0例北方汉族IgA肾病患者 (对其中 93例患者进行 2～ 6年的随访。)及北方汉族健康献血者 14 5例 ,盐析法提取外周血基因组DNA ,PCR 限制性片段长度多态性法确定UG基因G3 8A基因型 ,分析不同基因型与IgA肾病临床、病理及预后的关系。结果　 (1)IgA肾病患者UG基因的 3种基因型 (3 8AA、3 8AG和 3 8GG)与健康对照者间差异无显著性 (P >0 0 5)。 (2 ) 3种基因型与IgA肾病患者的性别、肾穿刺时的年龄、血尿、蛋白尿、肾功能、血清IgA水平及病理间无显著关系。 (3 )相对于其他基因型 ,3 8AA型预后差 (OR =2 3 7,95%CI =1 12～ 5 0 1,χ2 =8 2 48,P <0 0 1)。结论　UG基因G3 8A基因多态性与中国北方汉族人群IgA肾病的发病及临床无关 ,3 8AA基因型可能是IgA肾病慢性化进展的危险因子之一。     

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。     

Prothrombin A19911G and G20210A polymorphisms' role in thrombosis

The prothrombin G20210A polymorphism, which correlates with the plasmatic prothombin levels, is the second genetic risk factor for deep venous thrombosis (DVT), although its prothrombotic role is mild. Recently, the prothrombin A19911G polymorphism, also associated with slight variations of the prothrombin level, has been suggested to modulate the thrombotic risk of the G20210A polymorphism in a preliminary study including few patients and controls. Our study evaluated the effect of the A19911G polymorphism in the arterial and venous thrombotic risk of the prothrombin 20210G/A genotype, analysing 204 consecutive DVT patients and 204 matched controls. Moreover, we analysed 213 carriers of the 20210G/A genotype (152 with DVT, 26 with arterial thrombosis and 35 healthy subjects) and 10 homozygous 20210 A/A carriers. We developed a simple method to simultaneously determine the genotype of both polymorphisms. In accordance with our case/control study, the A19911G polymorphism did not play a significant role in the development of DVT. Analysis of 120 20210 A alleles demonstrated a complete linkage disequilibrium with the 19911 A allele. These polymorphisms (alone or combined) did not modify the risk of arterial thrombosis. However, the 19911A/G genotype slightly increased the risk of developing DVT in carriers of the 20210G/A genotype (OR 3.34 vs 5.86), supporting that the prothrombin 19911 polymorphism could modulate the risk of the G20210A polymorphism in developing DVT.     

The relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis

ABSTRACT

Objective: To investigate the relationship between gene polymorphism of MTRR A66G and lower extremity deep venous thrombosis (DVT).

Methods: Two hundred and two patients with DVT as experimental group and 240 normal adults (control group) were enrolled in this study and white blood cells were collected, respectively. Polymorphism of the 66 loci in MTRR gene was detected by polymerase chain reaction-sequence-specific primers (PCR-SSP) in two groups. The frequency of genotype and allele distribution of each group was compared.

Results: The frequency of AA, AG and GG genotypes in 66 sites of MTRR gene were 26.76%, 4 3.66% and 29.58% in DVT group and 43.57%, 44.28% and 12.14% in control group, respectively. There was no significant difference in the distribution frequency between two groups (χ?=?3.2, P?>?.5).

Conclusions: The gene polymorphism of MTRR A66G may not be an independent genetic risk factor in DVT in China.     

Interleukin 17A rs4711998 A>G polymorphism was associated with a decreased risk of esophageal cancer in a Chinese population

Esophageal cancer is the eighth most common cancer and sixth leading cause of cancer‐associated death worldwide. Besides environmental risk factors, genetic factors might play an important role in the esophageal cancer carcinogenesis. We conducted a hospital‐based case–control study to evaluate the genetic effects of functional single nucleotide polymorphisms (SNPs) in the interleukin 17A (IL17A) gene on the development of esophageal cancer. A total of 380 esophageal squamous cell carcinoma (ESCC) cases and 380 controls were recruited for this study. The genotypes were determined using a custom‐by‐design 48‐Plex SNPscan Kit. IL17A rs4711998 A>G polymorphism was associated with the decreased risk of ESCC. When the IL17A rs4711998 AA homozygote genotype was used as the reference group, the AG genotype was associated with a significantly decreased risk for ESCC (AG vs. AA: adjusted odds ratio 0.72, 95% confidential interval 0.53–0.98, P = 0.039). However, there was no significant association between the other five SNPs and ESCC risk. Stratified analyses indicated that a significantly decreased risk of ESCC associated with the IL17A rs4711998 A>G polymorphism was evident among younger patients and patients who never smoking or drinking. These findings indicated that functional polymorphism IL17A rs4711998 A>G might contribute to ESCC susceptibility. However, our results were obtained with a limited sample size; the power of our analysis was low. Future larger studies with more rigorous study designs of other ethnic populations are required to confirm current findings.     

Susceptibility to refractory ulcerative colitis is associated with polymorphism in the hMLH1 mismatch repair gene

The hMLH1 gene lies in the linkage susceptibility region to inflammatory bowel disease (IBD) on 3p21. A single nucleotide polymorphism, 655A>G, in exon 8 of the gene causes an I219V change in the MLH1 protein. To test whether hMLH1 may confer susceptibility to ulcerative colitis (UC), we investigated an association between the 655A>G polymorphism and the disease. DNA-based technologies were used to analyze the 655A>G polymorphism in 201 UC patients and 126 healthy ethnically matched controls. The comparison of the allelic frequencies of the 655A>G polymorphism in UC patients and healthy controls did not show significant differences. However, genotype frequencies at the hMLH1 655 position were found to be significantly different when patients with and without refractory UC were compared. This was mainly attributable to a higher level of homozygosity for the G allele in refractory UC patients. Almost 5 times as many (4.9 times) refractory UC patients carried the GG genotype compared with nonrefractory patients (P < 0.0001). The present study provides evidence that the hMLH1 gene is involved in genetic susceptibility to refractory UC. If confirmed by other studies, the GG genotype at position 655 of the hMLH1 gene may represent a useful predictive factor for the clinical management of UC patients.     

Distinct association of factor V-Leiden and prothrombin G20210A mutations with deep venous thrombosis in Tunisia and Lebanon

Factor V G1691A (FV-Leiden) and prothrombin (PRT) G20210A single nucleotide polymorphisms (SNPs) were associated with venous thrombosis among Caucasians. We assessed the contribution of both SNPs to the genetic susceptibility of deep venous thrombosis (DVT) among Lebanese and Tunisian patients. Subjects comprised 198 DVT patients and 540 healthy controls from Lebanon and 126 Tunisian DVT patients and 197 control subjects; FV-Leiden (MnlI) and PRT G20210A (HindIII) genotyping was done by PCR-RFLP. While the prevalence of FV-Leiden mutant A allele and the G/A and A/A genotypes were significantly higher among DVT patients from Lebanon and Tunisia, the association of PRT G20210A with DVT was pronounced among Lebanese but not Tunisian patients. The prevalence of PRT G20210A mutant A allele (P < 0.001 vs. P = 181) and G/A genotype (P < 0.001 vs. P = 0.994) was significantly higher among Lebanese but not Tunisians, respectively. While FV-Leiden was a common genetic risk factor for DVT in both communities, the contribution of PRT G20210A to the genetic susceptibility of DVT differed among Lebanese and Tunisians, which underscores the need to determine prothrombotic gene polymorphisms associated with DVT among Arab and Mediterranean basin communities.     

PAI-1 promoter 4G/5G genotype as an additional risk factor for venous thrombosis in subjects with genetic thrombophilic defects

Impaired fibrinolysis as a result of increased plasminogen activator inhibitor-1 (PAI-1) levels in plasma is a common finding in patients with deep vein thrombosis (DVT). A 4G/5G polymorphism in the promoter region of the PAI-1 gene has been reported to influence the levels of PAI-1. The 4G allele was found to be associated with higher plasma PAI-1 activity (act), but contradictory results on the incidence of the 4G allele in DVT patients have been reported. The aim of this study was to analyse whether the PAI-1 promoter 4G/5G genotype increases the risk of venous thrombosis in subjects with thrombophilic defects, and to determine the distribution of the PAI-1 4G/5G genotype and its relation to plasma PAI-1 levels in 190 unrelated patients with DVT in comparison with a control group of 152 healthy subjects. No differences between the 4G/5G allele distribution in the DVT group (0.43/0.57) and in the control group (0.42/0.58) were observed. However, the presence of the 4G allele significantly increased the risk of thrombosis in patients with other thrombophilic defects. Significantly higher PAI-1 levels were observed in DVT patients than in the controls. Our results also showed significant differences in the plasma levels of PAI-1 antigen (ag) and PAI-1 act among the 4G/5G genotypes in DVT patients. A multivariate analysis revealed that, in the DVT group, PAI-1 ag levels were influenced by the 4G allele dosage, triglyceride levels and body mass index (BMI). The influence of the 4G allele dosage on PAI-1 levels was independent of the triglyceride levels and BMI. In the control group, no significant correlation between PAI-1 levels and 4G allele dosage was observed. In conclusion, the PAI-1 promoter polymorphism was found to have an influence on PAI-1 levels in DVT patients and on the risk of venous thrombosis in subjects with other genetic thrombophilic defects.     

血管紧张素原基因启动子区域单核苷酸多态与高血压并发冠心病的关系

目的　研究在中国南方汉人群中 ,血管紧张素原基因 (angiotensinogen ,AGT)启动子区域 2 17位和 2 0位上的二种单核苷酸多态与高血压病 (EH)并发冠心病的关系。方法　运用多重SNaPshot反应 ,对 2 0 5例EH并发冠心病患者、185例EH患者和 185名健康对照者进行G 2 17A和A 2 0C多态基因分型。结果　G 2 17A多态的基因型分布在EH并发冠心病组 (AA =8、AG =71、GG =12 6 )和对照组 (AA =8、AG =37、GG =14 0 )之间有显著性差异 (P =0 0 0 5 ) ;A、G等位基因频率与对照组相比亦有显著性差异 (A 2 1 2 2 %、G 78 78%比A 14 32 %、G 85 6 8% ,P =0 0 12 ) ;A 2 0C多态的基因型分布 (CC、AC、AA)及C、A等位基因频率在二组间的差异无显著性 (分别为CC =5、AC =4 9、AA =15 1比CC =2、AC =6 1、AA =12 2 ,P =0 0 97;C 14 39%、A 85 6 1%比C 17 5 7%、A 82 4 3% ,P=0 2 2 6 )。在男性EH并发冠心病组中 ,G 2 17A和A 2 0C多态的基因型分布及其等位基因频率与对照组相比均有显著性差异 (G 2 17A :AA =7、AG =5 3、GG =86比AA =6、AG =2 8、GG =97,P =0 0 2 2 ;A 2 2 95 %、G 77 0 5 %比A 15 2 7%、G 84 73% ,P =0 0 2 2。A 2 0C :CC =3、CA =2 7、AA =116比CC =2、CA =4 3、AA =86 ,P =0 0 2 3;C 11 30 %     

Cigarette smoking, carrier state of A or G allele of 46A>G and 79C>G polymorphisms of beta2-adrenergic receptor gene, and the risk of coronary artery disease

BACKGROUND: Coronary artery disease (CAD) is a multifactorial disorder which results from the interactions between a number of genetic and non-genetic factors. Beta-adrenergic receptors are cell-surface receptors which activate adenylyl cyclase by coupling to G proteins. The 46A>G and 79C>G polymorphisms of the beta2-adrenergic receptor gene (ADRB2) have been associated with altered response to sympathetic stimulation. AIM: To assess the relationship between 46A>G and 79C>G polymorphisms of the ADRB2 gene and CAD as well as the associations between these polymorphic variants and traditional risk factors, e.g. cigarette smoking, hypercholesterolaemia, hypertension and overweight or obesity, in determining the risk of CAD. METHODS: The study population consisted of 207 individuals (white Polish Caucasians aged 20-55 years): 98 patients with angiographically documented CAD (with more than 50% diameter stenosis of at least one of the major coronary vessels) and 109 blood donors with no signs of CAD. The analysis of genetic polymorphisms was performed by means of PCR-RFLP. RESULTS: The genotype frequencies of both analysed genes in the studied groups were compatible with Hardy-Weinberg equilibrium. We observed higher frequency of the 46A allele in CAD patients than in controls. We also found a tendency to higher prevalence of 46A allele carriers (subjects with genotypes AA+AG) in the CAD group compared to the control group. We did not find any differences in the distribution of genotypes and alleles of 79C>G polymorphism between patients and controls. Multivariate analysis showed that smoking and overweight were independent risk factors of CAD in patients. We found a synergistic effect between carrier state of the 46A allele or 79G allele and smoking, which influences the CAD risk. The 46A allele carriers who smoke as well as carriers of the 79G allele who smoke were much more frequent in the CAD group than in controls. The incidence of 46A allele carriers with hypercholesterolaemia is also higher in patients than in the blood donor group. CONCLUSION: Obtained results indicate a synergistic effect between cigarette smoking and carrier state of 46A allele or 79G allele of ADRB2 in determining the risk of CAD.     

Functional effect of the p22phox -930A/G polymorphism on p22phox expression and NADPH oxidase activity in hypertension

Oxidative stress induced by superoxide is implicated in hypertension. NADPH oxidase is the main source of superoxide in phagocytic and vascular cells, and the p22phox subunit is involved in NADPH oxidase activation. Recently we reported an association of -930A/G polymorphism in the human p22phox gene promoter with hypertension. This study was designed to investigate the functional role of this polymorphism in hypertension. We thus investigated the relationships between the -930A/G polymorphism and p22phox expression and NADPH oxidase-mediated superoxide production in phagocytic cells from 70 patients with essential hypertension and 70 normotensive controls. Genotyping of the polymorphism was performed by restriction fragment length polymorphism. NADPH oxidase activity was determined by chemiluminescence assays, and p22phox mRNA and protein expression was measured by Northern and Western blotting, respectively. Compared with hypertensive subjects with the AA/AG genotype, hypertensive subjects with the GG genotype exhibited increased (P<0.05) phagocytic p22phox mRNA (1.26+/-0.06 arbitrary unit [AU] versus 0.99+/-0.03 AU) and protein levels (0.58+/-0.05 AU versus 0.34+/-0.04 AU) and enhanced NADPH oxidase activity (1998+/-181 counts/s versus 1322+/-112 counts/s). No differences in these parameters were observed among genotypes in normotensive cells. Transfection experiments on vascular smooth muscle cells showed that the A-to-G substitution of this polymorphism produced an increased reporter gene expression in hypertensive cells. Nitric oxide production, as assessed by measurement of serum nitric oxide metabolites, was lower in GG hypertensive subjects than in AA/AG hypertensive subjects. In conclusion, these results suggest that hypertensive subjects carrying the GG genotype of the p22phox -930A/G polymorphism are highly exposed to NADPH oxidase-mediated oxidative stress.     

Tissue factor promotor polymorphism -603 A/G is associated with myocardial infarction

Tissue factor (TF), the main initiator of the extrinsic coagulation cascade is expressed in atherosclerotic lesions and contributes to coronary thrombus formation in myocardial infarction (MI). Circulating TF reflects intravascular TF activation but also adds to prothrombotic activation. Because the G allele of the TF promotor polymorphism -603 A/G is associated with monocytic mRNA expression we evaluated its association with myocardial infarction, based on a recessive deleterious effect assumption. Patients with MI (MI; n=793) and age and sex matched control subjects without coronary artery disease (C; n=340) undergoing coronary angiography were included. In patients with MI, the -603 G (MI: 76%, C: 70%) allele was prevalent compared to the control group (P=-0.04). Multivariate analysis revealed an odds ratio of 1.44 (confidence interval 1.07-1.93). Carriage of the -603 G allele is associated with an increased risk for myocardial infarction. Because higher plasma TF concentrations are found in -603 G carriers enhanced TF expression may be the mechanism underlying this association.     

COX-2 polymorphisms -765G →C and -1195A→G and colorectal cancer risk

AIM： TO determine the possible modulating effect of the COX-2 polymorphisms, -765G→C and -1195A→G, on the risk of colorectal cancer （CRC） in a Dutch population. METHODS： This case-control study includes 326 patients with CRC and 369 age- and gender-matched controls. Genotypes of the COX-2 polymorphisms -7dEG→C and -1195A→G were determined by polymerase chain reaction-based restriction fragment length polymorphism. COX-2 genotypes and haplotypes were analyzed and odds ratios with 95% confidence intervals were estimated by logistic regression. RESULTS： The -765GG genotype was associated with an increased risk of developing CRC （OR, 1.45; 95% CI, 1.03-2.04）. No significant difference was observed in the genotype distribution of the -1195A→G polymorphism between patients and controls. The GG/AC haplotype was present significantly less often in patients than in controls （OR 0.44; 95% CI, 0.22-0.85）. When the AC, AG and GG haplotypes were investigated separately, the AC haplotype showed a tendency to be less frequent in patients than in controls （OR（AG/AC） 0.78; 95% CI, 0.57-1.06）. CONCLUSION： The -765GG genotype is associated with an increased risk of developing CRC and the G6/ AC haplotype seems to protect against CRC. These findings suggest a modulating role for the COX-2 polymorphisms -765G→C and -1195A→G in the development of CRC in a Dutch population.     

男性早发性冠心病与血管紧张素原基因启动子区域-217G/A和-152G/A多态

目的:研究血管紧张素原(angiotensinogen,AGT)基因启动子区域的-217G/A和-152G/A多态与上海地区汉族男性早发性冠心病(CAD)的相关性。方法:采用多重SNaPshot反应,在100例男性早发性CAD患者和100名健康男性对照者中,对AGT基因启动子区域的-217G/A和-152G/A多态进行基因分型。结果:-217G/A多态AA、AG和GG基因型在CAD组中的分布与对照组相比有显著性差异(P=0.039),CAD组的A等位基因频率较对照组亦显著增加(P=0.012),A等位基因携带者早发性CAD的发病危险是非携带者的1.913倍(95%CI1.151～3.182)。-152G/A多态的基因型分布在2组间的差异无统计学意义(P=0.154),其A、G等位基因频率2组相比有差异(P=0.044)。在多支病变组中,-217G/A多态的基因型分布及其等位基因频率2组相比均有显著性差异(分别为P=0.010和P=0.005),且A等位基因携带者发生多支病变的危险是非携带者的2.307倍(95%CI1.274～4.179)。结论:在上海地区的汉族男性人群中,AGT基因-217G/A和-152G/A多态可能是其早发性CAD的遗传性危险因素,且-217G/A多态可能还与冠状动脉粥样硬化的病变程度相关。     

Enzyme-to-enzyme channeling in the early steps of glycolysis in rat pancreatic islets

+49 A/G polymorphism of CTLA-4 gene has been suggested to be associated with type 1 diabetes in some populations. However, a functional significance of the +49 A/G polymorphism is unknown, because it is believed the polymorphism does not affect the function of the CTLA-4 molecule. In this study, we examined the +49 A/G polymorphism of the CTLA-4 gene in 30 Japanese type 1 diabetic patients (14 type 1B and 16 type 1A) and 40 non-diabetic subjects in a case-control study, and stratified patients according to genotype of the polymorphism. The distribution of genotype frequencies differed between type 1 diabetic patients and controls (p<0.01). When the subjects were subdivided into type 1A and type 1B subgroups, a significant difference in G allele frequency was found only between type 1B patients and controls, whereas G allele frequency tended to be higher in type 1A diabetic patients than controls. Type 1B patients displayed more severe metabolic decompensation (higher plasma glucose concentration, lower urinary C-peptide levels, higher insulin requirement, and higher serum amylase levels), and were found to be more prone to diabetic ketoacidosis than type 1A patients. After stratification by genotype, differences in urinary C-peptide and serum amylase levels between type 1A and type 1B patients were found to be due to differences in the GG genotype subgroup, whereas in the AG subgroup those differences disappeared. In conclusion, the +49 A/G polymorphism of CTLA-4 gene was associated with the occurrence of type 1B diabetes in a Japanese population, and type 1B diabetics with a GG genotype were associated with more severe cell dysfunction than their type 1A counterparts.