Association of CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms with myocardial infarction in South Indian population.

BACKGROUND: Cardiovascular diseases (CVDs) are the major cause of mortality and morbidity worldwide. Myocardial infarction (MI) is a complex multi-factorial, polygenic disorder arising from an interaction between genetic makeup of individuals and various environmental factors. CYP2C8, CYP2C9 and CYP2J2 gene involved in the metabolism of arachidonic acid, generates epoxyeicosatrienoic acids (EETs) that mediate dilation of coronary arteries improving post-ischemic cardiac contractile function, reduce vascular inflammation, and increase intravascular fibrinolysis. The study is aimed at analyzing the association of CYP2C8, CYP2C9 and CYP2J2 gene polymorphisms and MI risk in the South Indian population. METHODS: This retrospective study consisted of 287 MI patients, 279 risk control patients and 321 healthy individuals. Blood samples were collected from all the subjects and DNA was isolated using standard phenol-chloroform method. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and real time-polymerase chain reaction (RT-PCR) methods were used for genotyping. To test the potential independent association between polymorphisms and the risk of MI, Multiple-logistic regression analysis was performed. RESULTS: Our findings displayed a significant association between CYP2J2*7 (p=0.04; OR=2.0) polymorphism and MI while comparing cases with to risk controls. We did not observe any association of CYP2C8*2, CYP2C8*3, CYP2C9*2 and CYP2C9*3 with MI. CONCLUSION: Our results suggest that individuals with any conventional risk factor for MI along with CYP2J2*7 variant allele may be predisposed to risk of MI in South Indian population.

The dawn of hedgehog inhibitors: Vismodegib.

Cancer, one of the leading causes of death worldwide is estimated to increase to approximately 13.1 million by 2030. This has amplified the research in oncology towards the exploration of novel targets. Recently there has been lots of interest regarding the hedgehog (Hh) pathway, which plays a significant role in the development of organs and tissues during embryonic and postnatal periods. In a normal person, the Hh signaling pathway is under inhibition and gets activated upon the binding of Hh ligand to a transmembrane receptor called Patched (PTCH1) thus allowing the transmembrane protein, smoothened (SMO) to transfer signals through various proteins. One of the newer drugs namely vismodegib involves the inhibition of Hh pathway and has shown promising results in the treatment of advanced basal-cell carcinoma as well as medulloblastoma. It has been granted approval by US Food and Drug Administration's (US FDA) priority review program on January 30, 2012 for the treatment of advanced basal-cell carcinoma. The drug is also being evaluated in malignancies like medulloblastoma, pancreatic cancer, multiple myeloma, chondrosarcoma and prostate cancer. Moreover various Hh inhibitors namely LDE 225, saridegib, BMS 833923, LEQ 506, PF- 04449913 and TAK-441 are also undergoing phase I and II trials for different neoplasms. Hence this review will describe briefly the Hh pathway and the novel drug vismodegib.

Effect of eNOS polymorphisms on salbutamol evoked endothelium dependent vasodilation in South Indian healthy subjects.

BACKGROUND: The model of pulse plethysmograph using inhalational salbutamol 400 mcg is studied well to assess endothelium dependent vasodilation. Endothelial nitric oxide synthase (eNOS) gene polymorphism may influence the response to salbutamol in healthy subjects. AIM: To find the effect of polymorphisms 894G>T and -786T>C of eNOS gene on endothelium dependent vasodilation in healthy subjects. MATERIALS AND METHODS: One hundred and two south Indian healthy subjects of either sex, aged between 18 to 35 years were recruited for the study. The digital volume pulse (DVP)was measured by pulse plethysmograph before and after salbutamol 400mcg inhalation. Three predose and five postdose recordings of DVP were measured. The average change in the DVP parameters namely reflection index (RI) and stiffness index (SI) were determined. The eNOS894G>T and -786T>C gene polymorphism were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism. The percentage changes in RI and SI from predose baseline recordings were calculated and compared between the genotype groups. RESULTS: The genotype and allele frequency of study subjects were in Hardy-Weinberg equilibrium. The changes in DVP parameters were not significantly different between the genotype groups. CONCLUSION: eNOS polymorphism do not affect salbutamol evoked endothelium dependent vasodilation in the model of pulse plethysmograph in healthy subjects.