Tsering Stobdan

Endothelial nitric oxide synthase gene haplotypes and circulating nitric oxide levels significantly associate with risk of essential hypertension

Nitric oxide (NO), a potent vasodilator, plays a pivotal role in blood pressure regulation. Endothelial NO synthase gene (NOS3) polymorphisms influence NO levels. Here, we investigated the role of the -922A/G, -786T/C, 4b/4a, and 894G/T polymorphisms of the NOS3 and NO(x) levels in 800 consecutive unrelated subjects comprising 455 patients of essential hypertension and 345 controls. The polymorphisms were investigated independently and as haplotypes. Plasma NO(x) levels (nitrate and nitrite) were estimated by the Griess method. Genotype frequencies for the -786T/C, 4b/4a, and 894G/T polymorphisms differed significantly (P<0.001) between patients and controls and were associated with an increased risk of hypertension (OR=2.0, OR=3.8, OR=1.6, respectively). The 4-locus haplotypes ATaG (H1), ATaT (H2), and GCaG (H3) were significantly associated with essential hypertension and served as susceptible haplotypes (P<or=0.0001). On the other hand, haplotypes ATbG (H4) and GTbG (H5) were negatively associated with hypertension and served as protective haplotypes (P<0.0001). NO(x) levels were significantly lower in patients than controls (P<0.0001). The individual polymorphisms showed marginal association with NO(x) level; however, the susceptible haplotype H2 associated significantly with lower NO(x) levels in patients (P<0.001) and conversely the haplotype H4 with higher NO(x) levels in controls (P<0.001). In conclusion, the 4b/4a and likely -786T/C polymorphisms were identified as the determinants modifying the risk of hypertension. This study identifies the NOS3 variants and haplotypes as genetic risk factors and as useful markers of increased susceptibility to the risk of essential hypertension.

Structure and genetic diversity of natural populations of Morus alba in the trans-Himalayan Ladakh region.

Sequence-related amplified polymorphism markers were used to assess the genetic structure in three natural populations of Morus alba from trans-Himalaya. Multilocation sampling was conducted across 14 collection sites. The overall genetic diversity estimates were high: percentage polymorphic loci 89.66%, Nei’s gene diversity 0.2286, and Shannon’s information index 0.2175. At a regional level, partitioning of variability assessed using analysis of molecular variance (AMOVA), revealed 80% variation within and 20% among collection sites. Pattern appeared in STRUCTURE, BARRIER, and AMOVA, clearly demonstrating gene flow between the Indus and Suru populations and a geographic barrier between the Indus-Suru and Nubra populations, which effectively hinders gene flow. The results showed significant genetic differentiation, population structure, high to restricted gene flow, and high genetic diversity. The assumption that samples collected from the three valleys represent three different populations does not hold true. The fragmentation present in trans-Himalaya was more natural and less anthropogenic.

High Altitude Adaptation: Genetic Perspectives

The goal of this review is to highlight the underlying genetics that may explain complex traits associated with high altitude adaptation. The review covers the traditional candidate gene approach for identifying molecular variants having a functional role and associating with high altitude adaptation and disorders. We review some of the salient features of these candidate genes, debating their potential role in high altitude fitness. The advancement in high-throughput techniques in molecular genetics and the availability of large-scale catalogs of genetic variation in the public domain have provided a better platform for genome-wide scans for identifying genetic components for many traits. Current techniques such as whole-genome scans, admixture mapping using powerful tag SNPs, and the vast data available from human genome sequencing and the HapMap project may aid in a comprehensive understanding of genomic patterns of high altitude adaptation as well as disease-related research.

Nutritional Attributes and Health Application of Seabuckthorn ( Hippophae rhamnoides L.) – A Review

Seabuckthorn is a rich source of nutrients and bioactive components beneficial for human health. Fruit juice is rich in sugar, organic acids, amino acids, essential fatty acids, phytosterol, flavonoids, vitamins and mineral elements. There are 24 minerals and 18 kinds of free amino acids in seabuckthorn juice. The total quantity of phytosterol in seabuckhtorn exceeds soybean oil by 4-20 times. Seabuckthorn seed is a source of valuable oil characterized by high oleic acid content and one to one ratio of omega-3 and omega-6 fatty acids. The oil absorbs ultraviolet light and promotes healthy skin. The leaves contain many nutrients and bioactive substances such as carotenoids, free and esterified sterols, triterpenols, and isoprenols. Seabuckthorn has been used in traditional system of medicine for centuries. Beneficial effects of seabuckthorn on human health have been extensively investigated and substantiated by studies, suggesting a great potential of the plant for maintaining and promoting human health. Recent research has supported and extended the traditional uses of the plant for treatment of various diseases. The unique and valuable characteristics of seabuckthorn shrub serve as a storehouse for researchers in the field of biotechnology, nutraceutical, pharmaceutical, cosmetic and environmental sciences. Traditional usage coupled with commercial value and modern scientific research has immense scope to benefit the modern society from the lesser known shrub.

Significance of angiotensinogen gene haplotypes and genotypes combinations in hypertension

Objective Renin–angiotensin system gene polymorphisms are associated with essential hypertension; angiotensinogen gene variants are considered potential genetic risk factors. The aim of this study was to investigate the contribution of the G−6A, T174M, M235T polymorphisms, genotypic interactions, and haplotypes toward essential hypertension. Methods In a case–control design, 810 consecutive ethnically matched unrelated individuals comprising 450 hypertensive patients and 360 controls were recruited. Genotyping by polymerase chain reaction–restriction fragment length polymorphism, genotypes combinations, and haplotypes analyses were performed. Plasma renin activity and plasma aldosterone concentration were measured. Results The G−6A and M235T polymorphisms differed significantly (P = 0.007, odds ratio = 1.9, 95% confidence interval = 1.2–2.9; P < 0.0001, odds ratio = 3.7, 95% confidence interval = 2.3–5.7, respectively), wherein the −6A and 235T mutant alleles were over-represented in hypertensive patients (P < 0.0001, each). Genotypes combinations of six wild-type alleles versus the remaining resulted in odds ratio of 2.4 (P < 0.0001), further mutant alleles based combinations linearly correlated with systolic, diastolic, and mean blood pressure. Over-representation of the haplotypes, namely, A/174T, 174T/235T, A/235T, and A/174T/235T in hypertensive patients and G/174T, 174T/235M, G/235M, and G/174T/235M in controls, was identified as risk and protective haplotypes (P < 0.0001, each), respectively. The patients had significantly higher plasma aldosterone concentration and lower plasma renin activity (P < 0.0001), the former correlated with −6A and 235T alleles (P < 0.0001). Conclusion The interaction among G−6A, M235T and T174M polymorphisms in combinations or haplotypes emerged significant. These findings, conjoint with significant high plasma aldosterone concentration and low plasma renin activity, suggest low-renin hypertension in our study population.

The Genetic Aspects of Pre-eclampsia: Achievements and Limitations

Pre-eclampsia, a life-threatening disease during pregnancy, is a leading cause of global maternal mortality. Although there is substantial evidence of a genetic background, the complexity of the processes involved and nature of the maternal–fetal phenomenon do not make the search for the causative genes easy. Recent retrospective studies on the subject suggest the heritable allelic variations, particularly the utero-placental renin–angiotensin system with defective placental vascular development, could become the cornerstone for the genetics of pre-eclampsia and hence might well be associated with such defective development. Moreover, the role of immune mechanisms (immune maladaptation) deserves not to be ignored. Large-scale studies entailing genomewide scanning, sib-pair linkage analysis, and family-based association studies with appropriate power to detect genes with a lower relative risk are necessary to understand the puzzle of the disease. Moreover, recently, the importance of epigenetic features and the effect of imprinted genes related to trophoblast growth as well as fetal development on hypertension in pregnancy have been highlighted. All these possibilities are intuitively attractive and are supported by some circumstantial evidence. Although the consistent tenor of a series of papers instills some confidence, we need meticulously designed larger-scale investigations including large numbers of affected women and their babies to provide the analytic stringency essential to study the polygenic multifactorial basis of pre-eclampsia.

Antimicrobial activity of seed, pomace and leaf extracts of sea buckthorn ( Hippophae rhamnoides L.) against foodborne and food spoilage pathogens

The present study was conducted to evaluate the total phenolic content (TPC) and antibacterial properties of crude extracts of sea buckthorn ( Hippophae rhamnoides L.) pomace, seeds and leaves against 17 foodborne pathogens. The methanolic extract of leaves exhibited high total phenolic content (278.80 mg GAE/g extract) and had low minimum inhibitory concentration (MIC) value of 125 μg/ml against Listeria monocytogenes . Salmonella typhimurium strain was found to be resistant against all tested extracts. The antilisterial activity of the methanolic extract of leaves was tested on carrots. Bacterial enumeration was significantly reduced by 0.15 to 0.31, 0.26 to 1.72 and 0.59 to 4.10 log cfu/g after 0 to 60 min exposure when treated with 125, 2500 and 5000 μg/ml extract, respectively. Thus, in addition to its use as a functional food ingredient, leaves extract from sea buckthorn (SBT) can possibly be used as a biosanitizer in food industries. Key words: Antimicrobial activity, Hippophae, Listeria monocytogenes , natural sanitizer, seabuckthorn.

Cloning and nucleotide sequence of a novel cry gene from Bacillus thuringiensis.

A cry1Ab-type gene was cloned from a new isolate of Bacillus thuringiensis by PCR. When restriction pattern was compared with that of known genes it was found to have additional restriction site for ClaI. Nucleotide sequencing and homology search revealed that the toxin shared 95% homology with the known Cry1Ab proteins as compared to more than 98% homology among the other reported Cry1Ab toxins. The gene encoded a sequence of 1177 amino acids compared to 1155 amino acids encoded by all the other 16 cry1Ab genes reported so far. An additional stretch of 22 amino acids after the amino acid G793 in the new toxin sequence showed 100% homology with several other cry genes within cry1 family. Homology search indicated that the new cry1Ab-type gene might have resulted by nucleotide rearrangement between cry1Ab and cry1Aa/cry1Ac genes.

Research progress on the medicinal and nutritional properties of sea buckthorn (Hippophae rhamnoides) – a review

Summary Common sea buckthorn, Hippophae rhamnoides L. (Elaeagnaceae), is a small fruit tree widely distributed throughout Europe and Asia. Because H. rhamnoides plants are actinorhizal and tolerant of abiotic stresses, they grow in nutritionally-poor environments where it is difficult to grow other crops. Furthermore, sea buckthorn is rich in vitamins, unsaturated fatty acids, and phenolic compounds, and is used for medicinal purposes and as food in some parts of the World. In this review, we discuss (i) the pharmaceutical efficacy of H. rhamnoides; (ii) research on the sugars and acids contents of H. rhamnoides fruit, because it is part of the diet in some cultures and also shows promise as a functional food; and (iii) the various fruit phenotypes of sea buckthorn found in India and Russia because a high level of genetic diversity is important for improving fruit quality and yield. Few reviews on the medicinal and nutritional properties of H. rhamnoides have been published in the field of horticultural science. Sharing knowledge on this topic will contribute to the goal of improving the characteristics of sea buckthorn and increasing fruit production.

CYP11B2 gene haplotypes independently and in concurrence with aldosterone and aldosterone to renin ratio increase the risk of hypertension

OBJECTIVES Aldosterone synthase produces aldosterone, which regulates electrolytes and thereby blood pressure. Polymorphisms in aldosterone-synthase gene (CYP11B2) may associate with heterogeneous aldosterone production and hypertension. Hence, we investigated -344T/C, Iw/Ic polymorphisms of CYP11B2, plasma renin activity (PRA) and aldosterone concentration (PAC). DESIGN AND METHODS Consecutive ethnically-matched 450 hypertensive patients and 360 controls were screened by PCR-RFLP for genotypes and haplotypes; PRA and PAC were measured. RESULTS The Iw/Ic polymorphism distribution differed significantly between the two groups (LRT chi(2)=15.8, df=2, P=0.000). The mutant allele-Ic and genotype-Ic/Ic were overrepresented in patients (35% versus 27% and 13% versus 7%). Overrepresentation of T-Ic haplotype in patients was identified as risk haplotype (P=0.000). Patients had significantly higher PAC and aldosterone-to-renin ratio (ARR; P=0.000), which was Ic-allele dependent. CONCLUSIONS The haplotype T-Ic associated with hypertension susceptibility. Correlation between Ic-allele and raised ARR likely serve in hypertension management.