Single nucleotide polymorphism of CD40 in the 5′-untranslated region is associated with ischemic stroke

Objectives

Ischemic stroke is influenced by both environmental and genetic factors. The CD40/CD40L system is related to proinflammatory and prothrombogenic responses, which are involved in the pathophysiology of ischemic stroke. The aim of this study was to evaluate association between the CD40 -1C/T single nucleotide polymorphism (SNP) and ischemic stroke in a Chinese population.

Methods

We conducted a case–control study including 286 ischemic stroke patients and 336 controls. CD40 -1C/T SNP was genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing methods, and evaluated its relevance to ischemic stroke susceptibility.

Results

Significantly increased ischemic stroke risk was found to be associated with the T allele of CD40 -1C/T (OR = 1.273, 95% CI = 1.016–1.594). The frequencies of CT and TT/CT genotypes of CD40 -1C/T in ischemic stroke patients were significantly higher than those of controls, respectively (for CT: OR = 2.350, 95% CI = 1.601–3.449; for TT/CT: OR = 2.148, 95% CI = 1.479–3.119). And, similar results were obtained after adjusting non-matched variables. We found that the frequency of carried T genotypes (TT and TT/CT) was significantly increased in patients with history of stroke compared with patients without (for TT: OR = 6.538, 95%CI = 1.655–25.833; for TT/CT: OR = 3.469, 95%CI = 1.031–11.670), respectively.

Conclusions

The findings suggested that the CD40 -1C/T polymorphism might contribute to the susceptibility to ischemic stroke in the Chinese population, and might be associated with history of previous stroke.     

Common variant in FUT2 gene is associated with levels of vitamin B12 in Indian population

Vitamin B₁₂ is an essential micronutrient synthesized by microorganisms. Mammals including humans have evolved ways for transport and absorption of this vitamin. Deficiency of vitamin B₁₂ (either due to low intake or polymorphism in genes involved in absorption and intracellular transport of this vitamin) has been associated with various complex diseases. Genome-wide association studies have recently identified several common single nucleotide polymorphisms (SNPs) in fucosyl transferase 2 gene (FUT2) to be associated with levels of vitamin B₁₂—the strongest association was with a non-synonymous SNP rs602662 in this gene. In the present study, we attempted to replicate the association of this SNP (rs602662) in an Indian population since a significant proportion has been reported to have low levels of vitamin B₁₂ in this population. A total of 1146 individuals were genotyped for this SNP using a single base extension method and association with levels of vitamin B₁₂ was assessed in these individuals. Regression analysis was performed to analyze the association considering various confounding factors like for age, sex, diet, hypertension, diabetes mellitus and coronary artery disease status. We found that the SNP rs602662 was significantly associated with the levels of vitamin B₁₂ (p value < 0.0001). We also found that individuals adhering to a vegetarian diet with GG (homozygous major genotype) have significantly lower levels of vitamin B₁₂ in these individuals. Thus, our study reveals that vegetarian diet along with polymorphism in the FUT2 gene may contribute significantly to the high prevalence of vitamin B₁₂ deficiency in India.     

Relationship between chemokine (C–X–C motif) ligand 12 gene variant (rs1746048) and coronary heart disease: Case–control study and meta-analysis

The goal of our study is to evaluate the contribution of CXCL12 rs1746048 (hg19, chr10:44775574) to the risk of CHD in Han Chinese, and to summarize its role in CHD through meta-analysis of existing studies among various ethnic groups. Significant association is observed between rs1746048-C and an increased risk of CHD in Han Chinese (χ² = 5.41, df = 1, P = 0.02). Post hoc analysis reveals an even stronger association of rs1746048 with the risk of CHD for subjects aged 65 years or older (genotype: χ² = 8.39, df = 2, P = 0.015; allele: χ2 = 9.13, df = 1, P = 0.003, odd ratio (OR) = 1.91, 95% confidential interval (CI) = 1.25–2.91). A break down analysis by gender shows that rs1746048 is likely a CHD risk factor under the recessive model in males (CC + CT versus TT: P = 0.05, χ² = 3.59, df = 1, OR = 1.72, 95% CI = 1.00–3.04). In addition, a meta-analysis of ten studies among over 107,000 individuals confirms that rs1746048 is a risk factor of CHD (P < 0.0001, OR = 1.12, 95% CI = 1.09–1.15) and this agrees with the findings of our case–control study in Han Chinese.     

Therapeutic angiogenesis for revascularization in peripheral artery disease

Therapeutic angiogenesis for peripheral artery disease (PAD), achieved by gene and cell therapy, has recently raised a great deal of hope for patients who cannot undergo standard revascularizing treatment. Although pre-clinical studies gave very promising data, still clinical trials of gene therapy have not provided satisfactory results. On the other hand, cell therapy approach, despite several limitations, demonstrated more beneficial effects but initial clinical studies must be constantly validated by larger randomized, multi-center, double-blinded, placebo-controlled trials. This review focuses on previous and recent gene and cell therapy studies for limb ischemia, including both experimental and clinical research, and summarizes some important papers published in this field. Moreover, it provides a short comment on combined gene and cell therapy approach on the example of heme oxygenase-1 overexpressing cells with therapeutic properties.     

Applications of Biocatalysis to Biotechnology

β-lactam antibiotics (e.g. penicillins, cephalosporins) are of major clinical importance and contribute to over 40% of the total antibiotic market. These compounds are produced as secondary metabolites by certain actinomycetes and filamentous fungi (e.g. Penicillium, Aspergillus and Acremonium species). The industrial producer of penicillin is the fungus Penicillium chrysogenum. The enzymes of the penicillin biosynthetic pathway are well characterized and most of them are encoded by genes that are organized in a cluster in the genome. Remarkably, the penicillin biosynthetic pathway is compartmentalized: the initial steps of penicillin biosynthesis are catalyzed by cytosolic enzymes, whereas the two final steps involve peroxisomal enzymes. Here, we describe the biochemical properties of the enzymes of β-lactam biosynthesis in P. chrysogenum and the role of peroxisomes in this process. An overview is given     

Association between rs10118757(A/G) in methylthioadenosine phosphorylase gene and coronary artery disease in Chinese Hans

Studies focusing on the association of gene methylthioadenosine phosphorylase (MTAP) with the risk of coronary artery disease (CAD) and myocardial infarction (MI) are limited.     

GSTM1, GSTT1, GSTP1, and GSTA1 genetic variants are not associated with coronary artery disease in Taiwan

Background and objective

The genetic variants of xenobiotic-metabolizing enzymes, such as those encoded by glutathione-S-transferase (GST) genes, may be associated with the risk of coronary artery disease (CAD). To investigate the genetic factors for CAD, we examined the GSTM1, GSTT1, GSTP1, and GSTA1 genotypes in a CAD cohort in Taiwan.

Methods

Our study included 458 CAD participants and 209 control participants who received coronary angiography to assess CAD. The severity of CAD was defined as the number of coronary vessels with 50% or greater stenosis. Sequence variation of the GSTM1 and GSTT1 genes was determined using a polymerase chain reaction (PCR). The GSTP1 (Ile105Val), and GSTA1 (-69C > T) genetic variants were identified using a combination of PCR and restriction fragment length polymorphism analysis. Logistic regression analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals.

Results

Among the GST genetic variants examined, the GSTT1 null genotype was more prevalent in CAD participants with 3 stenosed vessels than in control participants (OR = 1.64, P = .02). This association was no longer observed after adjusting for age, sex, smoking, alcohol use, diabetes mellitus, and serum levels of total cholesterol and high-density lipoprotein cholesterol (OR = 1.28, P = .40). Both univariate and multivariate logistic regression analyses found no significant associations between CAD and the other genetic variants, either separately or in combination. In addition, no effects of interactions between the genotypes and environmental factors, such as cigarette smoking, were significantly associated with the risk of CAD.

Conclusion

The GST genetic variants examined were not associated with susceptibility to CAD in our Taiwanese cohort. This null association requires further confirmation with larger samples.     

Association study between of Tie2/Angiopoietin-2 and VEGF/KDR pathway gene polymorphisms and vascular malformations

Vascular malformations (VMs) are common congenital and neonatal dysmorphogenesis. VMs mostly occur sporadically with a few exceptions of inheritability. Tie2/angiopoietins-2 (Ang-2) and VEGF/KDR pathways are known to be involved in normal and pathogenic angiogenesis. Our study was aimed to test the contribution of these pathway gene variants to VMs. A total of 8 variants were found among 103 VM patients and 142 healthy controls. These variants comprised rs638203, rs639225, rs80338908 and rs80338909 in Tie2 gene, rs1870377 and rs2305949 in KDR gene, rs79337921 and rs34590960 in ANTXR1 gene. Our results indicated that rs638203 (p = 0.029) and rs639225 (p = 0.018) in Tie2 gene were associated with VM. A further bioinformatics analysis suggested the rs638203-G and rs639225-G might cause an abnormal splicing of Tie2 gene into to a defective protein. Our results identified two novel Tie2 gene polymorphisms with genetic susceptibility to VMs, although future functional validation of the two polymorphisms is warranted in the future.     

Human C-reactive protein gene polymorphism and metabolic syndrome are associated with premature coronary artery disease

The aim of this study was to investigate the association between C-reactive protein (CRP) gene polymorphism and metabolic syndrome (MetS) with premature coronary artery disease (PCAD). 116 patients with PCAD (58 with MetS and 58 without MetS) and 119 controls were included in the study. CRP gene + 1059 G>C polymorphism was analyzed by polymerase chain reaction. Serum hs-CRP was measured using high-sensitivity enzyme-linked immunosorbent assay. Carriers of C allele of the CRP + 1059 G>C polymorphism had 3.37 fold increased risk to develop MetS in patients with PCAD. In addition CRP gene and hs-CRP levels were independent risk factors for PCAD and MetS. The present study provides new evidence that the presence of CRP + 1059 G>C polymorphism and hs-CRP levels are independent determinants of PCAD and MetS in Egyptians. The results of our study suggest a synergistic effect of CRP C allele with classical risk factors such as hypertension, obesity, dyslipidemia and MetS.