Thrombosis Research Institute India

Bangalore, India

Thrombosis Research Institute India

Bangalore, India

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Shanker J.,Thrombosis Research Institute India | Rao V.S.,Thrombosis Research Institute India | Ravindran V.,Thrombosis Research Institute India | Dhanalakshmi B.,Thrombosis Research Institute India | And 3 more authors.
Thrombosis and Haemostasis | Year: 2012

Adiponectin and leptin link metabolic disorders and coronary artery disease (CAD). We analysed their relationship with CAD, classical risk factors and biomarkers in 287 CAD patients (cases) and 477 unaffected family members (controls) selected from the Indian Atherosclerosis Research Study (IARS). Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity markers. Novel biomarkers were measured according to manufacturer recommendations. Adverse clinical events were recorded through telephonic follow-up. Cases showed lower adiponectin levels (4684.62 ± 190.73 ng/ml) than controls (5768.86 ± 152.87 ng/ml) (p=1.58X10-5); Leptin levels were higher in affected males (12.47 ± 1.32 ng/ml) than in male controls (9.53 ± 1.19 ng/ml, p=0.017). Adiponectin 1st quartile showed significant protection against CAD in females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01, p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin levels. Adipokines showed opposing association trend with lipids, inflammatory and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity markers. Cases with recurrent event and controls who developed new cardiac event during follow up showed high adiponectin levels (p<0.05). A model that combined adiponectin, leptin and conventional risk factors yielded the best 'C' index (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed relatively poor survival curve as compared to the bottom Adiponectin tertile group. In conclusion, our findings strengthen the reported association between low adiponectin, high leptin, obesity-related metabolic disturbances and incident CAD in Asian Indians. © Schattauer 2012.


Maitra A.,Thrombosis Research Institute India | Shanker J.,Thrombosis Research Institute India | Dash D.,Thrombosis Research Institute India | Sannappa P.R.,Thrombosis Research Institute India | And 6 more authors.
Journal of Genetics | Year: 2010

We investigated the promoter polymorphisms of the pituitary growth hormone gene (GH1) and exon 3 deletion polymorphism (GHRd3) in its receptor gene (GHR) in 299 angiographically proven patients with coronary artery disease (CAD) and 231 asymptomatic controls enrolled in the ongoing Indian Atherosclerosis Research Study. Real time PCR based analysis of the GHR variant showed significant association of the GHRd3 deletion allele with CAD (OR 0.48, 95% CI: 0.30-0.76, P = 0.0014) and a dominant model of inheritance (Akaike information criterion = 482). The deletion allele showed significant association with high plasma HDL-c levels (P = 0.001). Sequencing of the proximal promoter region of GH1 revealed 12 novel polymorphisms and a TAGA haplotype constituted by the functional SNPs rs2005171, rs11568828, rs2005172 and rs6171, that showed significant association with CAD alone (adjusted OR of 3.31 (95% CI = 1.33-8.29, P = 0.011) and in CAD patients with diabetes (P = 0.019). Mean standardized height was associated with three of the four haplotype-tagging SNPs in the cohort (P ≤ 0.03). Eleven of the 12 polymorphic promoter SNPs contributed to 14.7% of variation in height in females in the whole dataset (P = 0.029). CAD patients with history of stroke exhibited marginally significantly lower mean height as compared to rest of the cohort (P < 0.006). In conclusion, genetic polymorphisms in the GHR gene and its ligand, GH1, may modulate the risk of CAD in the Asian Indian population. © 2010 Indian Academy of Sciences.


Shanker J.,Thrombosis Research Institute India | Maitra A.,Thrombosis Research Institute India | Arvind P.,Thrombosis Research Institute India | Nair J.,Thrombosis Research Institute India | And 7 more authors.
Translational Biomedicine | Year: 2012

Background and Objectives: Asian Indians show an inherent predisposition to premature Coronary Artery Disease (CAD) with a strong family history and therefore serve as a suitable population for identifying novel genes linked to CAD. We performed pilot linkage analysis on a subset of Asian Indian families selected from the Indian Atherosclerosis Research Study (IARS) to identify putative loci linked to CAD. Methods & Findings: We performed linkage study on six multiplex families consisting of 31 affected sibling pairs (ASPs). Families were ascertained through the proband who had angiographically confirmed CAD, with age at onset < 60 years for males and <65 years for females. Linkage mapping set v 2.5-MD10, comprising of 400 fluorescent labeled microsatellite markers were genotyped in 31 ASPs. Quantitative trait loci (QTL) analysis was carried out for sixteen atherothrombotic biomarkers and non parametric linkage analysis was performed by affected sibpair method. There was suggestive evidence of linkage at 4q21.21, 6q22.33, 6q23, 6q24.2 and 8q24.1 to CAD (Logarithm of Odds - LOD score ≥ 1; p<0.05). Bioinformatics analysis of significant linkage peaks identified key genes associated with inflammation and immune response. QTL analysis revealed suggestive evidence of linkage to Xp22.3 locus for total cholesterol (LOD =1.7) and at various loci on chromosomes 1,2,4,11 and X for Fibrinogen, Interleukin 2, Apolipoprotein A1, High density lipoprotein cholesterol and Apolipoprotein B (LOD >1; p<0.05), respectively. Conclusion: Novel loci on chromosome 4,6 and 8 has shown suggestive evidence of linkage to CAD in this initial study; their role in the etio-pathogenesis of CAD remains to be established. © iMedPub.


PubMed | Thrombosis Research Institute India
Type: Journal Article | Journal: Thrombosis and haemostasis | Year: 2012

Adiponectin and leptin link metabolic disorders and coronary artery disease (CAD). We analysed their relationship with CAD, classical risk factors and biomarkers in 287 CAD patients (cases) and 477 unaffected family members (controls) selected from the Indian Atherosclerosis Research Study (IARS). Classical risk factors included diabetes, hypertension, dyslipidaemia and obesity markers. Novel biomarkers were measured according to manufacturer recommendations. Adverse clinical events were recorded through telephonic follow-up. Cases showed lower adiponectin levels (4684.62 190.73 ng/ml) than controls (5768.86 152.87 ng/ml) (p=1.58X10(-5)); Leptin levels were higher in affected males (12.47 1.32 ng/ml) than in male controls (9.53 1.19 ng/ml, p=0.017). Adiponectin 1st quartile showed significant protection against CAD in females when compared to 3rd (odds ratio [OR] 0.39, 0.16-0.92, p=0.032) or 4th (OR 0.32, 0.14-0.72; p=0.006) quartile group. Leptin 3rd quartile showed higher CAD risk in males as compared to 1st quartile group (OR 2.09, 1.09-4.01, p=0.028). Subjects with metabolic syndrome showed low adiponectin and high leptin levels. Adipokines showed opposing association trend with lipids, inflammatory and coagulation markers and strong correlation (r=-0.14 to 0.52) with obesity markers. Cases with recurrent event and controls who developed new cardiac event during follow up showed high adiponectin levels (p<0.05). A model that combined adiponectin, leptin and conventional risk factors yielded the best C index (0.890, 0.067-0.912). CAD patients in the top adiponectin tertile showed relatively poor survival curve as compared to the bottom Adiponectin tertile group. In conclusion, our findings strengthen the reported association between low adiponectin, high leptin, obesity-related metabolic disturbances and incident CAD in Asian Indians.


PubMed | Thrombosis Research Institute India
Type: Comparative Study | Journal: Journal of genetics | Year: 2011

We investigated the promoter polymorphisms of the pituitary growth hormone gene (GH1) and exon 3 deletion polymorphism (GHRd3) in its receptor gene (GHR) in 299 angiographically proven patients with coronary artery disease (CAD) and 231 asymptomatic controls enrolled in the ongoing Indian Atherosclerosis Research Study. Real time PCR based analysis of the GHR variant showed significant association of the GHRd3 deletion allele with CAD (OR 0.48, 95% CI: 0.30-0.76, P = 0.0014) and a dominant model of inheritance (Akaike information criterion = 482). The deletion allele showed significant association with high plasma HDL-c levels (P = 0.001). Sequencing of the proximal promoter region of GH1 revealed 12 novel polymorphisms and a TAGA haplotype constituted by the functional SNPs rs2005171, rs11568828, rs2005172 and rs6171, that showed significant association with CAD alone (adjusted OR of 3.31 (95% CI = 1.33-8.29, P = 0.011) and in CAD patients with diabetes (P = 0.019). Mean standardized height was associated with three of the four haplotype-tagging SNPs in the cohort (P 0.03). Eleven of the 12 polymorphic promoter SNPs contributed to 14.7% of variation in height in females in the whole dataset (P = 0.029). CAD patients with history of stroke exhibited marginally significantly lower mean height as compared to rest of the cohort (P < 0.006). In conclusion, genetic polymorphisms in the GHR gene and its ligand, GH1, may modulate the risk of CAD in the Asian Indian population.

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