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Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case–control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non‐DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real‐time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is a common systemic vasculitis of childhood. Although it has been almost 6 decades since Dr. Tomisaku Kawasaki reported the first case series of KD, the underlying cause remains a mystery. KD is a self-limiting disease. However, a dreaded complication is development of coronary artery abnormalities (CAAs). KD is the most common cause of acquired heart disease in children in the developed world and is being increasingly reported from developing countries too. Over the years, significant observations have been made about epidemiology of KD. It usually affects children below 5, has male preponderance and has significantly higher incidence in North East Asian countries. While several hypotheses have been proffered for etiology of KD, none have been conclusive. These include associations of KD epidemics in Japan and the United Stated with changes in tropospheric wind patterns suggesting windborne agents, global studies showing peaks of incidence related to season, and increased rates in populations with a higher socioeconomic profile related to hygiene hypothesis and vaccination. Furthermore, the selflimiting, febrile nature of KD suggests an infectious etiology, more so with sudden decline noted in cases in Japan with onset of COVID-19 mitigation measures. Finally, single nucleotide polymorphisms have been identified as possible risk alleles in patients with KD and their significance in the pathogenesis of this disease are also being defined. The purpose of this review is to elucidate the puzzling associations of KD with different environmental factors. Looking at patterns associated with KD may help us better predict and understand this disease. [ABSTRACT FROM AUTHOR]

The objective of this study was to calculate the extent and decay of linkage disequilibrium (LD) in 96 crossbred Vrindavani cattle genotyped with Bovine SNP50K Bead Chip. After filtering, 43,821 SNPs were retained for final analysis, across 2500.3 Mb of autosome. A significant percentage of SNPs was having minor allele frequency of less than 0.20. The extent of LD between autosomal SNPs up to 10 Mb apart across the genome was measured using r2 statistic. The mean r2 value was 0.43, if pairwise distance of marker was less than10 kb and it decreased further to 0.21 for 25–50 kb markers distance. Further, the effect of minor allele frequency and sample size on LD estimate was investigated. The LD value decreased with the increase in inter-marker distance, and increased with the increase of minor allelic frequency. The estimated inbreeding coefficient and effective population size were 0.04, and 46 for present generation, which indicated small and unstable population of Vrindavani cattle. These findings suggested that a denser or breed specific SNP panel would be required to cover all genome of Vrindavani cattle for genome wide association studies (GWAS). [ABSTRACT FROM AUTHOR]

Stroke is one of the world's leading causes of disability and death. Antiplatelet agents are administered to acute ischemic stroke patients as secondary prevention. Clopidogrel involves biotransformation by cytochrome P450 (CYP) enzymes into an active metabolite, and single nucleotide polymorphisms (SNPs) can influence the efficacy of this biotransformation. Despite the therapeutic advantages of aspirin, there is significant inter-individual heterogeneity in response to this antiplatelet drug. In this clinical review, the recent advances in the biomarkers of antiplatelet agents in acute ischemic stroke are discussed. The studies reviewed herein highlight the clinical relevance of antiplatelet resistance, pharmacotherapy of antiplatelet agents predicting drug response, strategies for identifying aspirin resistance, pharmacogenetic variants of antiplatelet agents, miRNAs, and extracellular vesicles (EVs) as biomarkers toward the personalized approach in the management of acute ischemic stroke. The precise pathways contributing to antiplatelet resistance are not very well known but are presumably multi-factorial. It is essential to understand the clinical relevance of clopidogrel and aspirin-related single nucleotide polymorphism (SNPs) as potential predictive and prognostic biomarkers. Prasugrel is a next-generation antiplatelet agent that prevents ADP-platelet activation by binding irreversibly to P2Y12 receptor. There are sporadic reports of prasugrel resistance and polymorphisms in the Platelet endothelial aggregation receptor-1 (PEAR1) that may contribute to a change in the pharmacodynamics response. Ticagrelor, a direct-acting P2Y12-receptor antagonist, is easily absorbed and partly metabolized to major AR-C124910XX metabolite (ARC). Ticagrelor's primary active metabolite, ARC124910XX (ARC), is formed via the most abundant hepatic cytochrome P450 (CYP) enzyme, CYP3A4, and CYP3A5. The integration of specific biomarkers, genotype as well as phenotype-related data in antiplatelet therapy stratification in patients with acute ischemic stroke will be of great clinical significance and could be used as a guiding tool for more effective, personalized therapy. [ABSTRACT FROM AUTHOR]

Introduction: Genetic factors may play a role in the susceptibility of intracerebral hemorrhage (ICH). The present case-control study hypothesized that genetic polymorphisms in tumor necrosis factor- α (TNF-α) gene may affect the risk of ICH.Materials and Methods: In this study, we investigated the association of four single nucleotide polymorphisms (-308G/A, +488G/A, -857C/T, and -1031T/C) within TNF-α gene promoter and their haplotypes with the risk of ICH in a North Indian population. Genotyping was determined by using the SNaPshot method for 100 ICH patients and 100 age and sex-matched ICH-free controls. Conditional logistic regression analysis with adjusting multiple demographic and risk factor variables was used to calculate the strength of association between TNF-α gene polymorphisms and risk of ICH. Haplotypes were reconstructed using PHASE 2.0, and patterns of linkage disequilibrium (LD) analysis were performed using Haploview version 4.2 software.Results: TNF-α +488G/A gene polymorphism was found to be independently associated with the risk of ICH under dominant [GG + GA vs. AA] (OR = 3.1; 95% CI = 1.2-8.2; P = 0.001) and allelic [G vs. A] (OR = 2.2; 95% CI = 1.2-4.2; P = 0.007) models. However, no significant association between -308G/A, -857C/T, and -1031T/C gene polymorphisms and risk of ICH was observed. Haplotype analysis showed that 308A-488G-857C-1031T and 308G-488A-857T-1031T haplotypes were significantly associated with an increased risk of ICH. Strong LD was observed for + 488G/A and -857C/T TNF-α polymorphisms (D' = 0.72, r2= 0.01).Conclusion: Our findings suggest that the TNF-α +488G/A polymorphism may be an important risk factor for ICH, whereas -308G/A, -857C/T, and -1031T/C gene polymorphisms may not be associated with risk of ICH in North Indian population. [ABSTRACT FROM AUTHOR]

In present study, association of five single nucleotide polymorphisms (SNPs) of database rs109421300, rs43691049, rs109727821, rs109047657 and rs135678421 was investigated with milk minerals including calcium (Ca), phosphorus (P), copper (Cu), zinc (Zn), manganese (Mn), iron (Fe), sodium (Na), potassium (K) and constituents (fat and protein percentage) after adjusting the records with various significant non-genetic factors in crossbred (Vrindavani) cattle. The effect of rs109421300 pertaining to Diacylglycerol Acyltransferase (DGAT) gene located on BTA 14, was highly significant on fat percentage and significant on test day milk yield and non-significant on Ca, Cu, Mn, Zn, Fe, Na, K, test day milk yield and protein percentage. The AA genotypes of rs109421300 locus had significantly lower (2.96±0.17%) fat percentage than AG (4.64±0.22%), GG (4.62±0.27%) genotypes but simultaneously cows with AA genotypes had significantly highest (11.59±0.51 kg) test day milk yield than other two genotypes. At locus rs109727821, the manganese concentration was significantly highest (1.64±0.16 mg/l) for AG followed by AA (0.98±0.15 mg/l) and GG (0.77±0.24 mg/l) genotypes. The other SNPs had no significant association with traits under investigation. The existing association suggested possibilities to select animals for specific minerals and constituent traits in crossbred population. [ABSTRACT FROM AUTHOR]

Previously published studies that have examined whether the three polymorphisms, G894T, T786C, and 4b/a in the endothelial nitric oxide synthase (eNOS) gene, are associated with ischemic stroke (IS) have reported conflicting results. Thus, we performed a meta-analysis to examine the potential association between these three single nucleotide polymorphisms (SNPs) of the eNOS gene and IS risk. A literature search was carried out for eligible candidate gene studies published before August 05, 2015 in the PubMed, Embase, and Google Scholar databases. The following combinations of main keywords were used in our study: ('endothelial nitric oxide synthase') or ('eNOS') and ('G894T, 4b/a, and T786C') and ('polymorphism') or ('polymorphisms') and ('Ischemic Stroke' or 'IS') and ('Cerebral Infarction' or 'CI') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using fixed or random effects model. Meta-regression analysis was used to investigate the potential sources of heterogeneity. Begg's funnel plots were used to explore the publication bias, and heterogeneity was assessed by I2 test. Twenty seven case-control studies involving 6733 cases and 7305 controls were analyzed in our meta-analysis. Significant association was observed for G894T (OR = 1.17; 95% CI: 1.08 to 1.28; P< 0.001) and 4b/a (OR = 1.25; 95% CI: 1.13 to 1.39; P < 0.001) whereas a non-significant association was observed for T786C (OR = 1.11; 95% CI: 0.98 to 1.26; P =0.109) eNOS gene polymorphisms and IS. Our meta-analysis establishes that the G894T and 4b/a polymorphisms of eNOS gene are significantly associated with the risk of IS. However, a non-significant association was found between T786C polymorphism of the eNOS gene and IS risk. Further prospective large epidemiological studies need to be done to confirm these findings. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-beta 1 (TGF-β1) is a multifunctional pleiotropic cytokine involved in inflammation and pathogenesis of cerebrovascular diseases. There is limited information on the association between variations within the TGF-β1 gene polymorphisms and risk of ischemic stroke (IS). The aim of this study was to investigate the association of the TGF-β1 gene (C509T, G800A, and T869C) polymorphisms, and their haplotypes with the risk of IS in North Indian population. Methods: A total of 250 IS patients and 250 age- and sex-matched controls were studied. IS was classified using the Trial of Org 10172 in Acute Stroke Treatment classification. Conditional logistic regression analysis was used to calculate the strength of association between TGF-β1 gene polymorphisms and risk of IS. Genotyping was performed using SNaPshot method. Results: Hypertension, diabetes, dyslipidemia, alcohol, smoking, family history of stroke, sedentary lifestyle, and low socioeconomic status were found to be associated with the risk of IS. The distribution of C509T, G800A and T869C genotypes was consistent with Hardy-Weinberg Equilibrium in the IS and control groups. Adjusted conditional logistic regression analysis showed a significant association of TGF-β1 C509T (odds ratio [OR], 2.1; 95% CI; 1.2–3.8; P = 0.006), G800A (OR, 4.4; 95% CI; 2.1–9.3; P < 0.001) and T869C (OR, 2.6; 95% CI; 1.5–4.5; P = 0.001) with the risk of IS under dominant model. Haplotype analysis showed that C509-A800-T869 and T509-G800-C869 haplotypes were significantly associated with the increased risk of IS. C509T and T869C were in strong linkage disequilibrium (D’ =0.51, r2 = 0.23). Conclusion: Our results suggest that TGF-β1 polymorphisms and their haplotypes are significantly associated with the risk of IS in North Indian population. [ABSTRACT FROM AUTHOR]

In present investigation genetic variability in humoral response to classical swine fever (CSF) vaccination was explored. The aim of the study was to find association of 14 single nucleotide polymorphisms (SNPs) (IL-1β, MX1, IRF3 and SLA genes) with humoral response measured in terms of percentage inhibition of E2 antibody by competitive enzyme-linked immunosorbent assay. The post-vaccination response of CSF vaccination was low to moderate inDesipiglets ranged from 25.29% to 92.23% whereas it was moderate to high inDesi×Landracepiglets ranged from 69.30% to 100%. The response to CSF vaccination was significantly (P< 0.0001) differing inDesiandDesi×Landracepiglets. The mean percentage inhibition inDesipiglets was 62.73% but inDesi×Landracecross-bred it was 97.24%. None of the SNPs of present investigation was significantly associated with humoral immune response inDesipiglets. Two SNPs namely rs80937718 (SLA DQA1) and rs80929898 (SLA DQA1) were significantly (P< 0.01) affecting the humoral response of CSF vaccination inDesi×Landracepiglets. [ABSTRACT FROM PUBLISHER]

In the present study, polymorphisms at two single nucleotide polymorphisms (SNPs)  and one microsatellite locus of SLC11A1 gene were investigated for finding their association with susceptibility to bovine tuberculosis trait (tuberculin reaction) in Indian cattle. A total of 245 animals were tested with single intradermal tuberculin test for screening positive animals for tuberculin reaction. At rs109915208 locus very low polymorphism information content of 0.0454 was observed, whereas it was moderate (0.352) at rs109453173 locus of SLC11A1. At rs109915208 locus the genotypic as well as allelic frequencies were differing significantly (p-value < .05) in case–control animals where the odds ratio (OR) of ‘CC’verses‘CT’ genotype and the OR of ‘C’verses ‘T’ allele were approaching towards infinity, suggesting that animals having ‘CT’ genotype and ‘T’ allele were less susceptible for tuberculin reaction as compared to their contemporary genotype/allele. The significantly associated SNP was non-synonymous causing an amino acid change. [ABSTRACT FROM PUBLISHER]

Background: Interleukin-6 (IL-6), as one of the most typical pro-inflammatory and immunoregulatory cytokines, is believed to be associated with the genesis and maintenance of inflammatory response. Genetic association studies (GAS) that have investigated the association between Interleukin 6 (G174C and G572C) promoter gene polymorphisms and susceptibility to ischemic stroke (IS) which have produced contradictory and unconvincing results. Purpose: The aim of this meta-analysis is to provide a relatively comprehensive account of the association of IL-6 (G174C and G572C) polymorphisms with susceptibility to IS. Methods: A literature search was conducted using electronic database PubMed, Medline, and Trip database for all case-control studies investigating for association of IL-6 genetic polymorphisms with ischemic stroke published till August 30, 2014. The following combinations of main keywords were used: ('Interleukin- 6' or 'IL-6') and ('ischaemic stroke or 'cerebral infarction' or 'IS') and ('genetic polymorphism' or 'single nucleotide polymorphisms' or 'SNP'). Pooled Odds ratios (ORs) and 95% confidence intervals (CIs) were determined for IL-6 gene-disease association. Meta-analysis was carried out using Revman 5.3 software. Results: 16 case-control studies involving a total of 3,317 IS patients and 3,432 healthy controls for G174C polymorphism and 3 case-control studies with a total of 2,001 IS patients and 2,027 healthy controls for G572C IL-6 gene polymorphisms were included in a meta-analysis. For IL-6 G174C gene polymorphisms, no significant association was observed under dominant [GC + CC vs. GG: OR = 1.01, 95% CI: 0.77-1.34, P = 0. 92], recessive [CC vs. GG + GC: OR = 0.82, 95% CI: 0.40-1.70, P = 0. 59] and allelic model [C vs. G Allele: OR = 0.99, 95% CI: 0.74-1.31, P = 0. 93]. For IL-6 G572C, no significant association was observed under dominant [CC vs. GG + GC: OR = 0.99, 95% CI: 0.57-1.71, P = 0. 97], recessive [CC vs. GG + GC: OR = 0.93, 95% CI: 0.60-1.45, P = 0. 75] and allelic model [C vs. G Allele: OR = 0.95, 95% CI: 0.66-1.36, P = 0. 76]. Conclusion: This meta-analysis shows that IL-6 (G174C) and IL-6 (G572C) gene polymorphisms may not be associated with an increased susceptibility to IS. Further studies are required for confirmatory results. [ABSTRACT FROM AUTHOR]

Background: Stroke is the second most common cause of death and disability worldwide. It is a multi-factorial disease influenced by both environmental and genetic factors. Studies from the different ethnic regions of world have reported variable results on association of Apolioprotein E (APOE), Methylenetetrahydrofolate reductase (MTHFR), Endothelial Nitric Oxide Synthase (ENOS), Factor V Leiden (F5), Cytochrome P450 4F2 (CYP4F2), betafibrinogen and Phosphodiesterase 4D (PDE4D) gene in stroke. There has been substantial evidence from the European descent genetic studies showing that genetic risk of stroke varies as per specific subtypes of ischemic stroke. This study aims to test the hypothesis that above mentioned encoding gene polymorphisms are associated with stroke and to determine whether risk varies as per specific subtypes of stroke. Methods/Design: The study design would be case-control study. Six hundred cases with diagnosis of stroke and 600 age and sex matched controls will be recruited. Controls will be matched in 1:1 ratio. Baseline and demographic data will be collected in standardized data collection form. Four ml of blood will be collected in EDTA coated vial and will be used for DNA isolation. Genotyping will be done by using PCR-RFLP method. For the reconfirmation of RFLP results, PCR product of each genotype in triplet for all the selected polymorphism will be sent for DNA sequencing. Data will be analyzed using conditional logistic regression to determine odds ratio associated with the above genes. Discussion: This protocol will assess the association of above mentioned gene polymorphisms with ischemic stroke in North Indian Population. This study will also helpful to determine genetic component of stroke and whether variation in genetic risk as per different subtypes of stroke. [ABSTRACT FROM AUTHOR]

A total of 9 SNPs located in TFRC and ACK1 genes of SSC13q41 genomic region were examined for their association with the adhesion pattern of native Indian pigs using local isolate of diarrhoeagenic E. coli. Phenotypic evaluation of adhesion pattern of 150 pigs revealed 116 animals positive for adhesion, whereas 34 animals had non-adhesive phenotype. Among the adhesive animals, 6, 87 and 23 pigs were strongly adhesive, weakly adhesive and adhesive, respectively. PCR–RFLP study revealed 8 polymorphic SNPs with low to moderate PIC ranging from 7.39 to 37.25% and low to high heterozygosities (8–70%). The loci g.291 C > T, rs81218930 C > T, rs318751568 C > T of TFRC and g.93222 C > A g.94600 C > T of ACK1 showed significant departure from HWE. The genotypic frequencies of the SNPs as well as the haplotypes did not differ significantly (P > 0.05) across the adhesion patterns except one SNP (ACK1-g.107371 A > C). Among the g.107371 A > C genotypes observed, CA was associated with non-adhesive phenotype. Furthermore, TFRC mRNA expression levels were found to be significantly (P < 0.05) different among various adhesive phenotypes, whereas that of ACK1 was significantly (P < 0.05) different between non-adhesive and adhesive groups. The significant association of SNP (ACK1-g.107371 A > C), which was also previously reported to influence ETECF4 mediated diarrhoea susceptibility, implicates its wider application in genetic control of piglet diarrhoea. Furthermore, the up-regulation of TFRC gene expression in adhesive group supports its proposed role in activation of immune cells against E. coli and intracellular iron transport. [ABSTRACT FROM AUTHOR]

Aim: Toll-like receptor 2 (TLR2) and TLR4 genes play critical roles in host recognition of Mycobacterium bovis infection and initiation of innate and adaptive immune response. The present study was aimed at exploring the association of seven single nucleotide polymorphisms (SNPs) in TLR2 and TLR4 genes with susceptibility/resistance against bovine tuberculosis (bTB) infection in cattle. Materials and Methods: A case-control resource population of 35 positive and 45 negative animals was developed after screening with single intradermal tuberculin test for bTB. Resource population was screened for SNPs in TLR2 and TLR4 genes using polymerase chain reaction-restriction fragment length polymorphism. The PROC LOGISTIC procedure of SAS 9.3 was used to find an association of allelic and genotypic frequencies with bTB. Results: In TLR2 gene, two of SNPs under study (rs55617172 and rs68268253) revealed polymorphism while in the case of TLR4 gene all four SNPs under investigation (rs8193041, rs207836014, rs8193060, and rs8193069) were found to be polymorphic in case-control population. SNP locus rs55617172 in TLR2 gene was found significantly (p<0.01) associated with susceptibility/resistance to TB in cattle. Conclusion: These findings indicate the presence of SNPs in TLR2 and TLR4 genes in our resource population. Upon validation in independent, large resource population and following biological characterization, SNP rs55617172 can be incorporated in marker panel for selection of animals with greater resistance to bTB. [ABSTRACT FROM AUTHOR]

The article informs that Multiple criteria are being used across different geographies to identify a reinfection. Topics include well-defined and consistent definition for deciding what constitutes true SARSCoV-2 reinfection; and studying different approaches that are being used globally, the goal is to determine a criterion that is accurate and practical in its application on a scale in India.

• Haplotype structure was elucidated in Vrindavani cattle via sliding window approach. • Haplotype-based association analysis was undertaken with (re)production traits. • Haplotypes showed significant association with AFC, TLMY, PY, DD, ICP and SP. • Overlapping candidate genes revealed pathways affecting the (re)production performance. Haplotype-based association analysis promises to reveal important information regarding the effect of genetic variants on economic traits of interest. The present study aimed to evaluate the haplotype structure of Vrindavani cattle and explore the association of haplotypes with (re)production traits of economic interest. Genotyping array data of medium density (Bovine50KSNP BeadChip) on 96 randomly selected Vrindavani cows was used in the present study. Genotypes were called in GenomeStudio program while quality control was undertaken in PLINK using standard thresholds. The phenotypic traits used in the present study included age at first calving, dry days, lactation length, peak yield, total lactation milk yield, inter-calving period and service period. The haplotype structure of Vrindavani population was assessed, using a sliding window of 20 SNP with a shift of 5 SNPs at a time, in terms of the size of haplotype blocks regarding their length (in Kb) and frequency in chromosome-wise fashion. Haplotype blocks were assessed for possible association with important production and reproduction traits across three lactation cycles in Vrindavani cattle population. The first ten principal components were included in the model for haplotype-based association analysis to correct for stratification effects of assessed individuals. Multiple haplotypes were found to be associated with age at first calving, total lactation milk yield, peak yield, dry days, inter-calving period and service period. Various candidate genes were found to overlap haplotypes that were significantly associated with age at first calving (CDH18, MARCHF11, MYO10, FBXL7), total lactation milk yield (TGF, PDE1A, and COL8A1), peak yield (PPARGC1A, RCAN1, KCNE1, SMIM34 and MRPS6), dry days (CPNE4, ACAD11 and MRAS), inter-calving period (ABCG5, ABCG8 and COX7A2L) and service period (FOXL2 and PIK3CB). The putative candidate genes overlapping the significantly associated haplotypes revealed important pathways affecting the production and reproduction performance of animals. The identified genes and pathways may serve as good candidate markers to select animals for improved production and reproduction performance in future generations. [ABSTRACT FROM AUTHOR]