Vascular endothelial growth factor -634 G/C polymorphism and risk of cancer: an updated meta-analysis.

The association between vascular endothelial growth factor (VEGF) gene polymorphisms and risk of cancer has been investigated in several studies published previously; however, the individual results are inconclusive. Therefore, we performed a meta-analysis to establish evidence for an association between the VEGF -634 G/C polymorphism and risk of cancer. We searched PubMed, Medline, and Korean Studies Information Service System databases and identified 29 case-control studies, containing data of 25,324 individuals, for this meta-analysis. The odds ratio (OR) and 95% confidence interval (95%CI) were used to determine the strength of the association. Overall, no significant association was detected in the allele model (G allele vs C allele, OR = 0.98, 95%CI = 0.93-1.03), dominant model (G/G+G/C vs C/C, OR = 1.00, 95%CI = 0.90-1.11), or recessive model (G/G vs G/C+C/C, OR = 0.96, 95%CI = 0.89-1.03). The meta-analysis results suggest that the VEGF -634 G/C polymorphism may not be related to the development of cancer. However, additional studies with larger sample size are required in order to provide supporting evidence.

Assessment of CASP gene polymorphisms in periodontal disease.

Caspases (CASP) are intracellular proteases that play roles as mediators of apoptosis. Activation of caspase 3 is enhanced in chronic periodontitis. Thus, we hypothesized that single nucleotide polymorphisms (SNPs) of CASP genes might be associated with this condition in the Korean population. To investigate whether such polymorphisms might be involved in the development of periodontal disease, 51 patients and 33 control subjects were assessed. A total of 201 CASP gene SNPs were analyzed with genotypes being determined using and Axiom(TM) genome-wide human assay. SNPStats and SPSS 18.0 were used for the analysis of genetic data and logistic regression models were utilized to evaluate odds ratios, 95% confidence intervals, and P values. Of the 201 SNPs, only three (rs12108497, rs4647602, and rs113420705, all in the CASP3 gene) were significantly associated with chronic periodontitis (P < 0.05). The minor allele frequencies of these SNPs were higher in the patient group than in the control group. In addition, the TC and GT haplotypes formed by rs4647602 and rs113420705 were found to be associated with chronic this disease (TC haplotype, P = 0.0039; GT haplotype, P = 0.002). These results suggest that CASP3 gene polymorphisms may be associated with susceptibility to periodontal disease in the Korean population.

Effects of nicotine on apoptosis in human gingival fibroblasts.

AIM: Cigarette smoke is a complex mixture of more than 4700 chemical compounds including free radicals and oxidants and it is a world widely known problem to health. Nicotine is the major compound of tobacco and known as the cause of gingivitis and periodontitis. It induces intracellular oxidative stress recognized as the important agent in the damage of biological molecules. The aim of this study is to clarify the cytotoxic pathway of nicotine in human gingival fibroblasts (HGFs). METHODS: Human gingival fibroblasts stimulated by nicotine were used as an in vitro model. A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect cell viability and reactive oxygen species (ROS) generation was assessed with 2,7-dichlorofluoroscein diacetate (DCF-DA). Morphological change was detected by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay, stained with 4,6-diamidino-2-phenylindole (DAPI). To delineate the roles of extracellular signal-regulated kinase (ERK), P38 and c-Jun N-terminal kinase (JNK), Western blot and caspase-3 (CASP3) activity assay were performed. RESULTS: Exposure of the human gingival fibroblasts to nicotine reduced cell viability by time and dose dependent and increased the generation of ROS. It also showed morphological evidence of increased apoptosis, resulted in transient activation of JNK and ERK concomitant with activation of P38, and stimulated apoptosis as evidenced by CASP3 activation and Poly ADP ribose polymerase (PARP) cleavage. CONCLUSION: These results suggest that nicotine induces apoptosis through the ROS generation and CASP3 dependent pathways in HGFs.

Glutathione S-transferase M1 (GSTM1) polymorphism is associated with atopic dermatitis susceptibility in a Korean population.

Atopic dermatitis (AD) is a chronic pruritic skin condition affecting as much as 15% of children in industrialized countries. While the underlying pathophysiology of AD is not entirely understood, several studies have suggested that AD may mediated by oxidative stress. Glutathione S-transferases (GSTs) are a class of polymorphic enzymes that function to protect against oxidative stress. To identify any possible associations between GSTs polymorphisms and AD susceptibility, the prevalence of two specific polymorphisms -GSTM1 and GSTT1 (homozygous deletion vs. undeleted) - were quantified by multiplex PCR in 145 patients with AD and 267 healthy controls. In individuals with AD, GSTM1/GSTT1 polymorphisms were compared with family history of AD, age of disease onset, disease severity [per SCORing Atopic Dermatitis (SCORAD)], serum IgE level and presence of other allergic diseases. While the GSTM1-null genotype was found to be significantly associated with AD (P = 0.033, OR = 1.579, 95% CI = 1.037-2.403), the correlation between the GSTT1-null genotype and AD did not reach statistical significance (P = 0.577, OR = 1.125, 95% CI = 0.744-1.702). The GSTM1-null genotype was also found to be significantly associated with a childhood onset of AD, the absence of other allergic diseases, and a family history of AD. In combination, these results suggest that GSTM1 is associated with AD susceptibility in Korean subjects.