Association study of PCSK9 SNPs (rs505151 & rs562556) and their haplotypes with CVDs in Indian population.

BACKGROUND: Cardiovascular disease (CVD) has emerged as the most prevalent cause of death in India. Pro-protein Convertase Subtilisin/Kexin Type 9 (PCSK9) gene has been found to be associated with lipid levels and a biomarker for susceptibility of CVD. AIM: To study the association of PCSK9 SNPs rs505151 & rs562556 and their haplotypes with CVDs in the Indian population. SUBJECTS & METHODS: The present study comprised of 102 angiographically proven CVD patients & 100 healthy subjects. To study polymorphism, Polymerase Chain Reaction and Restriction Fragment Length Polymorphism (PCR-RFLP) method was used. Biochemical parameters were analysed by enzymatic methods or automated analysers. Haplotype analysis was done using SHEsis software. RESULTS: The dominant genetic model with an odds ratio (confidence interval) of 4.71 (2.59 - 8.5), (p value = .0001), shows the risk of CVDs. However, rs562556 (I474V) variant was not found to be associated with clinical parameters and risk of CVDs (p value >.05). Out of four haplotypes, H3 (G-A) was found to be associated with the CVDs (OR- 3.137, p value = .0001). CONCLUSION: This study concludes that G allele of rs505151 SNP (PCSK9) and the H3 (G-A) haplotype of rs505151 & rs562556 were found to be risk factors for CVDs in the Indian population.

Genetic variation in DPP-IV gene linked to predisposition of T2DM: A case control study.

Purpose: DPP-IV is a ubiquitously expressed cell surface protein that can be presented in soluble forms. It has recently gained medical importance as its inhibitors are widely being used as treatment of T2DM. The present research aims to resolve whether genetic variants of DPP-IV have association with susceptibility to T2DM. Method: Two variants of DPP-IV were detected in 100 controls and 100 T2DM by PCR-RFLP technique. Demographic characteristics were recorded. Clinical characteristics were analyzed by enzymatic method. Statistical analysis was performed using SPSS-21. Results: Demographic and clinical characteristics differ significantly between two groups. The genetic variation in SNP rs3788979 and SNP rs7608798, both in case and control, were in accordance with Hardy-Weinberg Equilibrium (p value > 0.05). Both SNPs rs3788979 and rs7608798 were significantly related to T2DM (p- < 0.05). Minor G allele of rs3788979 was linked with the susceptibility of T2DM (p-value-0.000; OR- 4.235). T allele of SNP rs7608798 conferred the risk of diabetes with OR-2.235. Conclusion: This is the first attempt to investigate the association of DPP-IV gene with T2DM in Indian population. The finding of study concludes that genetic variation in DPP-IV gene may considerably increase the risk of developing T2DM.

Light and temperature regulated terpene biosynthesis: hepatoprotective monoterpene picroside accumulation in Picrorhiza kurrooa.

Picrorhiza (Picrorhiza kurrooa) is an endangered medicinal plant with well-known hepatoprotective activity attributed to monoterpenoid picrosides. The present article details on regulatory genes of terpenoid metabolism, 3-hydroxy-3-methylglutaryl coenzyme A reductase (pkhmgr) and 1-deoxy-D-xylulose-5-phosphate synthase (pkdxs) from picrorhiza. Since no molecular information was available, these genes were cloned to full-length by degenerate primers and rapid amplification of cDNA ends, followed by cloning of the upstream sequences that showed the presence of core sequences for light and temperature responsiveness. Electrophoretic mobility shift assay confirmed binding of protein to these motifs. Expression of pkhmgr and pkdxs was up-regulated at 15 degrees C as compared to at 25 degrees C as well as under light as compared to dark conditions. Picrosides content exhibited the trend similar to gene expression. To rule out the possible limitation of carbon pool under dark condition, plantlets of picrorhiza were raised in vitro in Murashige and Skoog medium supplemented with 3% sucrose. Results showed similar up-regulation of both the genes and the higher picrosides content in in vitro raised plantlets in the presence of light. Data suggested the important roles played by light and temperature in regulating pkhmgr and pkdxs, and the picrosides level in picrorhiza.