Association of PON2 and PON3 polymorphism with risk of developing cataract

PurposeParaoxonases (PON) are calcium bound enzymes offering protection against oxidative stress by working as endogenous free-radical scavenging molecules. Oxidative stress has been implicated in pathophysiology of many diseases including cataract. Lens opacity is an age related disorder which is a principal cause of blindness in Pakistani population. Relationship of PON2 and PON3 polymorphism with genetic predisposition for incidence of cataract has not been investigated till date. Objective of the current study was to explore possible association between PON2 and PON3 polymorphism with incidence of cataract in local population.MethodsOur study design comprised of fifty-one cataractous and fifty-nine healthy individuals. Identification of single nucleotide polymorphism (SNP) at positions (C311S and G148A) for PON2 and C133A for PON3 was conducted using restriction fragment length polymorphism (RFLP).ResultsStatistical analysis revealed significant association of PON2 G148 allele with incidence of cataract. GG allele was found to be higher in cataract patients as compared to control (p < 0.001) suggesting distribution of PON2 G148A genotype and allele frequency is linked with cataractogenesis. There was no noticeable association between PON2 C311S and PON3 C133A. Significant difference was observed in distribution of 311CS/148A combined genotype with highest frequency in control individuals (88.89%), while 311S/148G combined genotypes showed the highest frequencies among the cataract patients (71.42%).ConclusionOur data suggests mutation at G148A might be related with incidence of cataract in studied population.     

Association of IL-12B rs3212227 and IL-6 rs1800795 Polymorphisms with Susceptibility to Cervical Cancer: A Systematic Review and Meta-Analysis

Background: Primary studies have shown that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms are associated with an increased risk of cervical cancer. However, conflicting results warrant a meta-analysis to obtain more precise estimates. Methods: A comprehensive literate search on PubMed, Web of Science, Scopus, CNKI, and SciELO was performed to collect all eligible studies up to November 10, 2019. The pooled odds ratios (OR) and 95% confidence intervals (CI) were used to calculate the risk. This meta-analysis was carried out by utilizing CMA software. Results: A total of eleven case-control studies including four studies on IL-12B rs3212227 and seven studies on IL-6 rs1800795 were selected. Pooled ORs revealed that the IL-6 rs1800795 polymorphism was significantly associated with an increased risk of cervical cancer (C vs. G: OR = 1.294, 95% CI 1.071-1.564, p= 0.007; CC vs. GG: OR = 1.633, 95% CI 1.059-2.520, p= 0.027; CC+CG vs. GG: OR = 1.312, 95% CI 1.048-1.643, p= 0.018; and CC vs. CG+GG: OR = 1.592, 95% CI 1.268-1.999, p≤0.001), but not IL-12B rs3212227 polymorphism. Stratified analysis by ethnicity revealed that both IL-12B rs3212227 and IL-6 rs1800795 polymorphisms were associated with risk of cervical cancer in Asian women. Conclusions: Our pooled data revealed that the IL-12B rs3212227 and IL-6 rs1800795 polymorphisms may be used to identify individuals at high risk of cervical cancer in Asian women.     

Matrix metalloproteinase 9 (MMP9) level and MMP9 -1562C>T in patients with obstructive sleep apnea: a systematic review and meta-analysis of case-control studies

BackgroundThe peripheral level of matrix metalloproteinase (MMP)-9 and polymorphism of MMP9 -1562C>T in patients with obstructive sleep apnea (OSA) remains controversial. Therefore, the aims of this systemic review and meta-analysis are to assess the MMP9 level in OSA patients and identify the relationship between MMP9 -1562C>T and OSA susceptibility.MethodsThis systematic review was performed following the PRISMA guideline. We searched for studies in major databases, identifying those indexed from inception to July 3, 2019 which related to MMP9 level, MMP9 -1562C>T and OSA. The pooled standardized mean differences (SMDs) and 95% confidence interval (CI) of MMP9 levels were calculated. In addition, the relationship between MMP9 -1562C>T and OSA susceptibility was assessed by three genetic models. The heterogeneity analysis and calculation of the pooled odds ratio (OR) were also performed, followed by quality assessment using the Newcastle-Ottawa Scale (NOS).ResultsIn sum, our review included 15 eligible studies regarding MMP9 level and three regarding MMP9 -1562C>T. The pooled results showed that peripheral level of MMP9 was increased in OSA patients (SMD = 1.37; 95% CI = 1.15–1.59). Furthermore, significant difference of MMP9 level can be found between severe and mild-to-moderate OSA patients (SMD = 28.17; 95% CI = 4.23–52.11) or between moderate-severe and mild OSA (SMD = 36.62; 95% CI = 12.19–61.04). However, no relationship was observed between MMP9 -1562C>T and OSA susceptibility in three genetic models (Homozygote model, OR = 1.37; 95% CI = 0.87–2.18); (Recessive model, OR = 1.42; 95% CI = 0.83–2.42); (Allele model, OR = 1.07; 95% CI = 0.96–1.18).ConclusionsThis systemic review and meta-analysis indicated that the level of MMP9 was increased in patients with OSA and this increase is relevant to OSA severity. Moreover, the relationship between MMP9 -1562 C>T and OSA susceptibility has currently not been proven by current merging values. Further analyses with larger sample size are required to verify these associations.     

A Study of Ser217Leu and Ala541Thr Polymorphism in the Men Afflicted with Prostate Cancer and in the Men being Suspicious of Prostate Cancer

Background and objective: Prostate cancer is one of the most widespread cancers among men throughout the world. In addition, it is the second cause of death after lung cancer. Occurrence of the prostate cancer is variable in various regions of the world. Solely, there are three known risk factors for the prostate cancer, including: Age, inheritance and ethnic origin. ELAC2 protein is a phosphodiesterase enzyme encoded by ELAC2 gene in human. This gene is placed on chromosome 17, and it is believed that product of the mentioned gene is an endonuclease contributed in puberty of mitochondrion’s tRNA. From clinical viewpoint, variables of ELAC2 gene such as Ser217Leu and Ala541Thr Missense mutations which are accompanied by hereditary prostate cancer (HPC2).Objective of this study is to investigate Ser217Leu (rs4792311) and Ala541Thr (rs5030739) polymorphisms in the individuals with prostate cancer or those who are suspicious of prostate cancer with family past record/history. Study method: In this study conducted by case-control method in 2018, 102 men with prostate cancer and 98 men being suspicious of prostate cancer out of 10 families referred to shahid Rajaei Hospital in Tonekabon county to study and check were investigated. After collection of data using questionnaire, sampling from individuals and performance of the rest steps, study of polymorphism was carried out by PCR sequencing technique, and the results were analyzed by Chromas software. Finding: Of the total studied 102 individuals, 44 individuals (43.1%) were homozygote for Ser217Leu mutation, 36 individuals (35.2%) were heterozygote and 22 individuals (21.5%) lacked Missense mutation. for Ala541Thr mutation, 18 ones (17.6%) were heterozygote and 84 ones (82.3%) lacked Missense mutation. For Ser217Leu mutation, out of 98 suspicious individuals, 21 individuals (21.4%) were homozygote. 6 individuals (6.1%) were heterozygote and 71 individuals (72.4%) lacked the mutation. For Ala541Thr mutation, 15 ones (15.3%) were homozygote and 84 ones (84.6%) lacked the studied mutation. Conclusion: Results of this research showed that, in the individuals with the prostate cancer, there is a relationship between Ser217Leu and Ala541Thr polymorphism of ELAC2 gene and/with prostate cancer, and the suspicious individuals gotten involved in the mutation must take action to prevent this cancer.     

Polymorphisms of insulin-like growth factor binding protein-3 as a predictor for risk and patient survival in esophageal squamous cell carcinoma

Background and purposeGenetic single nucleotide polymorphisms (SNP) play a critical role in the development of esophageal squamous cell carcinoma (ESCC). The aim of this study is to investigate the associations between insulin-like growth factor binding protein-3 (IGFBP-3) gene polymorphisms and ESCC patients risk and survival after definitive chemoradiotherapy (CRT).Materials and methodsWe undertook a case-control study to analyze two IGFBP-3 polymorphisms (rs2854744 A > C and rs2854746 G > C) in an Han Chinese population, by extraction of genomic DNA from the peripheral blood of 110 ESCC patients treated with CRT and 128 control participants, and performed IGFBP-3 genotyping using DNA sequencing.ResultsThe obtained results indicated that overall, no statistically significant association was observed in rs2854746 G > C. However, rs2854744 A > C genotype was at increased risk of ESCCs (P = 0.032; odds ratio (OR) = 1.201, CI 95%:1.014–1.423). Moreover, rs2854744 A > C genotype ESCCs were more significantly common in patients with tumor size of >6 cm than A allele ESCC and in cases of lower T stage. Furthermore, ESCC patients with rs2854744CC genotype have the poorer CRT response and shorter survival time than GG + GC genotype ESCC.ConclusionsIn conclusion, polymorphism in IGFBP-3 rs2854744 A > C might be a potential predictor of ESCC risk and patient survival. Nevertheless, further investigation with a larger sample size is needed to support our results.     

阻塞性睡眠呼吸暂停低通气综合征患者CYP3A4基因多态性的检测

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)CYP3A4基因的多态性,了解其对芬太尼类药物的敏感性及不同基因型的人群分布特征,指导临床个体化用药。方法对50例OSAHS患者进行CYP3A4基因的多态性检测,采静脉血,通过DNA抽提-PCR扩增-焦磷酸测序方法检测CYP3A4基因。结果野生纯合型型34例(68%),突变杂合型15例(30%),突变纯合型型1例(2%)。结论OSAHS患者中约2%为AA型,该型对芬太尼类药物极其敏感,术后有易发生窒息的风险,应高度警惕芬太尼类药物呼吸抑制的潜在风险。