An association study between transforming growth factor-β1 receptor 2 gene polymorphisms and essential hypertension / 中华预防医学杂志

<p><b>OBJECTIVE</b>To evaluate the association between two single nucleotide polymorphisms located in the promoter of transforming growth factor-β1 receptor 2 (TGFBR2) gene and hypertension in Han Chinese population.</p><p><b>METHODS</b>The subjects were recruited from the population of cluster sampling survey for essential hypertension (EH) in two townships of Yixing city, Jiangsu province in 2009. Overall, 2012 patients with hypertension and 2116 age (± 2 years) and sex-matched unrelated controls were selected. Epidemiological data, physical measurements results and serum glucose and lipid biomarker were collected and detected. Linkage disequilibrium (LD) analysis were applied and two tagging single nucleotide polymorphisms (tagSNP) in 5' upstream of TGFBR2 gene (rs6785358, -3779A/G; rs764522, -1444C/G) were selected for genotyping and analyzing for the association with hypertension.</p><p><b>RESULTS</b>The frequencies of AA, AG, GG in case and control of rs6785358 were 1455 (72.3%), 517 (25.7%), 40 (2.0%) and 1582 (74.8%), 490 (23.2%), 43 (2.0%) respectively, and CC, CG, GG of rs764522 were 1524 (75.7%), 464 (23.1%), 24 (1.2%) and 1654 (78.2%), 436 (20.6%), 26 (1.2%) respectively. SNP rs764522 was significantly associated with EH and OR (95%CI) were 1.17 (1.01 - 1.36) (P < 0.05) in dominant model after adjustment for confounding factors such as age, sex, glucose, lipids, smoking and alcohol drinking. Further stratification analysis by age, sex, smoking and alcohol drinking indicated that individuals carrying G allele (CG/GG genotype) of SNP rs764522 had higher susceptibility to EH than CC genotype (OR = 1.21, 95%CI: 1.01 - 1.45) (P < 0.05) in ≥ 55 years group. No statistical significance was detected in the distribution of genotypes and allele frequencies for SNP rs6785358 between cases and controls (P > 0.05). Haplotype analysis showed that no significant frequency difference of haplotype structured by rs6785358 and rs764522 was found between cases and controls (P > 0.05), and no significant blood pressure change was found between genotype variations of rs6785358 and rs764522 (P > 0.05).</p><p><b>CONCLUSION</b>SNP rs764522 of TGFBR2 gene is associated with increased risk of EH in elderly Han Chinese population.</p>

Silencing of signal transducer and activator of transcription 3 gene expression using RNAi enhances the efficacy of radiotherapy for laryngeal carcinoma in vivo / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the inhibitory effect of signal transducer and activator of transcription 3 (STAT3) shRNA generated by vector pSilence in conjunction with radiotherapy on laryngeal squamous cell carcinoma of nude mice xenograft tumor.</p><p><b>METHODS</b>The animal models of xenotransplanted human laryngeal carcinoma cell line Hep-2 were set up in 28 nude mice which were divided into 4 groups at random: the negative plasmid control group, the group that received pshSTAT3 (pGPU6/GFP/NeoshSTAT3) transfection, the radiation group, and the group of pshSTAT3 transfection combined with irradiation. Tumor volume was determined regularly. On the fifteenth day after termination of radiation treatment, the mice were sacrificed, the tumor weight was measured in all the groups, the inhibition rate for tumor growth was calculated and tumor growth curve was plotted. Meanwhile, the expressions of p-STAT3, B cell lymphoma 2 (bcl-2), p53, vascular endothelial growth factor (VEGF) protein and intratumor microvessel density (MVD) were observed by immunohistochemistry. Computer-assisted image analysis was used to obtain the results. Flow cytometry was used to detect the cell apoptosis rate.</p><p><b>RESULTS</b>There was a significant difference in tumor volume among the groups (P<0.01). The rate of tumor inhibition in the pshSTAT3 group, radiation group and pshSTAT3 plus radiation group was 19.68%, 34.76% and 67.70%, respectively. The p-STAT3 protein expression decreased significantly in the group of pshSTAT3 plus simple radiotherapy (P<0.01). The intratumoral MVD in the group of pshSTAT3 plus simple radiotherapy was significantly lower compared to the negative plasmid control group and the radiotherapy group (P<0.01), while the apoptosis rate was much higher (P<0.01). There was a positive correlation between the expressing of p-STAT3 and bcl-2, p53, VEGF and MVD (r value was 0.738, 0.727, 0.735, 0.691, all P<0.01), and there was a negative correlation concerning cell apoptosis rate. Moreover, a statistically positive association was present between MVD and p53, VEGF protein expression, respectively (r value was 0.784, 0.641, all P<0.01); and the correlation was negative between expression of bcl-2 and apoptosis rate (r=-0.883, P<0.01).</p><p><b>CONCLUSIONS</b>Using pshSTAT3 in conjunction with radiotherapy can significantly inhibit the growth of laryngeal carcinoma.</p>