Sydney D’Souza

Effect of 3-Month Yoga on Oxidative Stress in Type 2 Diabetes With or Without Complications: A controlled clinical trial

OBJECTIVE To assess the effect of yoga on anthropometry, blood pressure, glycemic control, and oxidative stress in type 2 diabetic patients on standard care in comparison with standard care alone. RESEARCH DESIGN AND METHODS The study involved 123 patients stratified according to groups with microvascular complications, macrovascular complications, and peripheral neuropathy and without complications and assigned to receive either standard care or standard care along with additional yoga for 3 months. RESULTS In comparison with standard care alone, yoga resulted in significant reduction in BMI, glycemic control, and malondialdehyde and increase in glutathione and vitamin C. There were no differences in waist circumference, waist-to-hip ratio, blood pressure, vitamin E, or superoxide dismutase in the yoga group at follow-up. CONCLUSIONS Yoga can be used as an effective therapy in reducing oxidative stress in type 2 diabetes. Yoga in addition to standard care helps reduce BMI and improve glycemic control in type 2 diabetic patients.

Population specific impact of genetic variants in KCNJ11 gene to type 2 diabetes: A case-Control and meta- Analysis study

Background and Objectives Potassium inwardly rectifying channel, subfamily J, member 11 (KCNJ11) gene have a key role in insulin secretion and is of substantial interest as a candidate gene for type 2 diabetes (T2D). The current work was performed to delineate the genetic influence of KCNJ11 polymorphisms on risk of T2D in South Indian population through case-control association study along with systematic review and meta-analysis. Methods A case-control study of 400 T2D cases and controls of South Indian origin were performed to analyze the association of KCNJ11 polymorphisms (rs5219, rs5215, rs41282930, rs1800467) and copy number variations (CNV) on the risk of T2D. In addition a systematic review and meta-analysis for KCNJ11 rs5219 was conducted in 3,831 cases and 3,543 controls from 5 published reports from South-Asian population by searching various databases. Odds ratio with 95% confidence interval (CI) was used to assess the association strength. Cochrans Q, I2 statistics were used to study heterogeneity between the eligible studies. Results KCNJ11 rs5215, C-G-C-C haplotype and two loci analysis (rs5219 vs rs1800467) showed a significant association with T2D but CNV analysis did not show significant variation between T2D cases and control subjects. Lower age of disease onset (P = 0.04) and higher body mass index (BMI) (P = 0.04) were associated with rs5219 TT genotype in T2D patients. The meta-analysis of KCNJ11 rs5219 on South Asian population showed no association on susceptibility to T2D with an overall pooled OR = 0.98, 95% CI = 0.83–1.16. Stratification analysis showed East Asian population and global population were associated with T2D when compared to South Asians. Conclusion KCNJ11 rs5219 is not independently associated with T2D in South-Indian population and our meta-analysis suggests that KCNJ11 polymorphism (rs5219) is associated with risk of T2D in East Asian population and global population but this outcome could not be replicated in South Asian sub groups.

Replication and Relevance of Multiple Susceptibility Loci Discovered from Genome Wide Association Studies for Type 2 Diabetes in an Indian Population

Aim Several genetic variants for type 2 diabetes (T2D) have been identified through genome wide association studies (GWAS) from Caucasian population; however replication studies were not consistent across various ethnicities. Objective of the current study is to examine the possible correlation of 9 most significant GWAS single nucleotide polymorphisms (SNPs) for T2D susceptibility as well as the interactive effect of these variants on the risk of T2D in an Indian population. Methods Case-control cohorts of 1156 individuals were genotyped for 9 SNPs from an Indian population. Association analyses were performed using logistic regression after adjusting for covariates. Multifactor dimensionality reduction (MDR) analysis was adopted to determine gene–gene interactions and discriminatory power of combined SNP effect was assessed by grouping individuals based on the number of risk alleles and by calculating area under the receiver-operator characteristic curve (AUC). Results We confirm the association of TCF7L2 (rs7903146) and SLC30A8 (rs13266634) with T2D. MDR analysis showed statistically significant interactions among four SNPs of SLC30A8 (rs13266634), IGF2BP2 (rs4402960), HHEX (rs1111875) and CDKN2A (rs10811661) genes. Cumulative analysis showed an increase in odds ratio against the baseline group of individuals carrying 5 to 6 risk alleles and discriminatory power of genetic test based on 9 variants showed higher AUC value when analyzed along with body mass index (BMI). Conclusion These results provide a strong evidence for independent association between T2D and SNPs for in TCF7L2 and SLC30A8. MDR analysis demonstrates that independently non-significant variants may interact with one another resulting in increased disease susceptibility in the population tested.

New molecular detection methods of malaria parasites with multiple genes from genomes.

For the effective control of malaria, development of sensitive, accurate and rapid tool to diagnose and manage the disease is essential. In humans subjects, the severe form of malaria is caused by Plasmodium falciparum (Pf) and Plasmodium vivax (Pv) and there is need to identify these parasites in acute, chronic and latent (during and post-infection) stages of the disease. In this study, we report a species specific and sensitive diagnostic method for the detection of Pf and Pv in humans. First, we identified intra and intergenic multiloci short stretch of 152 (PfMLS152) and 110 (PvMLS110) nucleotides which is present up to 44 and 34 times in the genomes of Pf and Pv respectively. We developed the single-step amplification-based method using isolated DNA or from lysed red blood cells for the detection of the two malaria parasites. The limit of detection of real-time polymerase chain reaction based assays were 0.1copyof parasite/μl for PfMLS152 and PvMLS110 target sequences. Next, we have tested 250 clinically suspected cases of malaria to validate the method. Sensitivity and specificity for both targets were 100% compared to the quantitative buffy coat microscopy analysis and real-time PCR (Pf-chloroquine resistance transporter (PfCRT) and Pv-lactate dehydrogenase (PvLDH)) based assays. The sensitivity of microscopy and real-time PCR (PfCRT and PvLDH primers) assays were 80.63%; 95%CI 75.22%-85.31%; p<0.05 and 97.61%; 95%CI 94.50%-99.21%; p<0.05 in detecting malaria infection respectively when compared to PfMLS152 and PvMLS110 targets to identify malaria infection in patients. These improved assays may have potential applications in evaluating malaria in asymptomatic patients, treatment, blood donors and in vaccine studies.

Categorical complexities of Plasmodium falciparum malaria in individuals is associated with genetic variations in ADORA2A and GRK5 genes

In the erythrocytes, malaria parasite entry and infection is mediated through complex membrane sorting and signaling processes. We investigated the effects of single-locus and multilocus interactions to test the hypothesis that the members of the GPCR family genes, adenosine A2a receptor (ADORA2A) and G-protein coupled receptor kinase5 (GRK5), may contribute to the pathogenesis of malaria caused by Plasmodium falciparum (Pf) independently or through complex interactions. In a case-control study of adults, individuals affected by Pf malaria (complicated n=168; uncomplicated n=282) and healthy controls (n=450) were tested for their association to four known SNPs in GRK5 (rs2230345, rs2275036, rs4752307 and rs11198918) and two in ADORA2A (rs9624472 and rs5751876) genes with malaria susceptibility, using techniques of polymerase chain reaction-restriction fragment length polymorphisms and direct DNA sequencing. Single-locus analysis showed significant association of 2 SNPs; rs5751876 (OR=3.2(2.0-5.2); p=0.0006) of ADORA2A and rs2230345 (OR=0.3(0.2-0.5); p=0.0006) of GRK5 with malaria. The mean of the serum creatinine levels were significantly higher in patients with variant GG (p=0.006) of rs9624472 in ADORA2A gene compared to AA and AG genotypes in complicated Pf malaria cases, with the G allele also showing increased risk for malaria (OR=1.3(1.1-1.6); p=0.017). Analyses of predicted haplotypes of the two ADORA2A and the four GRK5 SNPs have identified the haplotypes that conferred risk as well as resistance to malaria with statistical significance. Molecular docking analysis of evolutionary rs2230345 SNP indicated a stable activity of GRK5 for the mutant allele compared to the wild type. Further, generalized multifactor dimensionality reduction to test the contribution of individual effects of the six polymorphisms and higher-order interactions to risk of symptoms/clinical complications of malaria suggested a best six-locus model showing statistical significance. The study provides evidence for the role of ADORA2A and GRK5 that might influence the etiology of malaria infection.

Impact of KCNJ11 , TCF7L2 , SLC30A8 , IGF2BP2 , PPARG , SLC47A1 , STK11 , HHEX , KCNQ1 , CDKAL1 , FTO , CYP2C9 , ADIPOQ , CAPN10 gene polymorphisms on risk of type 2 diabetes and therapeutic response to sulfonylurea and metformin therapy

Type 2 Diabetes (T2D) represents a spectrum of metabolic disorders is genetically heterogeneous disease with multiple genes located on different chromosomes contributing to its susceptibility. Prevalence of T2D has increased sharply in recent years with more than 300 million people worldwide and 70 million in India. The application of molecular, genomic knowledge will provide new opportunities to explore the heterogeneity which patients clearly exhibit and provide a more accurate understanding of individual patients. Single nucleotide polymorphisms (SNPs) represent the most profuse form of genetic variation in humans which are gaining increased popularity and emerging as a new generation genetic markers. With several classes of drugs available to treat T2D its clinical response exhibits significant variation among individuals which exerts a huge impact on healthcare system and economic burden due to diabetes treatment. Pharmacogenetic research which assesses the role of genetic variants can be used in elucidating the nature of these variants on differential drug response. In the current study, we evaluated the association of KCNJ11, TCF7L2, SLC30A8, IGF2BP2, PPARG, SLC47A1, STK11, HHEX, KCNQ1, CDKAL1, FTO, CYP2C9, ADIPOQ, CAPN10 gene polymorphisms with T2D and response to sulfonylurea and metformin using PCR-RFLP, TETRA-ARMS and DNA sequencing techniques. Study subjects were 330 T2D patients who are on sulfonylurea (178) and metformin (152) treatment with age and sex matched normal healthy controls of south Indian origin. Allele frequencies, genotype and haplotype distribution were analyzed by chi-squared test. Logistic regression analysis was used to predict the effect of gene variants on treatment. Gene–gene interactions were analyzed by generalized multifactor dimensionality reduction method. Linkage disequilibrium between each pair of SNP loci, were estimated and plotted with JLIN. We have also performed a systematic review and Meta-Analysis of KCNJ11 rs5219 and PPARG rs1801282 SNPs on South Asian populations to clarify inconsistency in association results. Our analysis showed KCNJ11 rs5215, SLC30A8 rs1326634, TCF7L2 rs7903146 were associated with susceptibility to T2D. Multivariate regression analysis showed that TCF7L2 rs12243326 TT genotype, KCNJ11 rs5219 TT genotype were associated with response rate to sulfonylurea treatment and STK11 rs741765 GG genotype, SLC30A8 rs1326634 TT genotype were associated with response rate to metformin treatment.

Pneumomediastinum due to tracheal foreign body granuloma.

Primary tracheal masses are rare. Secondary masses of the trachea are commonly foreign body granuloma, intubation granuloma or viral granuloma. The differential diagnoses given in such cases include both benign and malignant lesions. The otolaryngologist is often asked to perform a biopsy of the lesion to arrive at a diagnosis. However, even malignant processes can cause a granulomatous reaction. The timely diagnosis of tracheal masses depends upon maintaining a high index of suspicion. A rare case of tracheal granuloma leading to pneumomediastinum in a 53-year-old female is presented. The clinical features, investigations and treatment are detailed. The tracheal granuloma was managed by excision through bronchoscopy and the pneumomediastinum was managed conservatively.