Thiruvananthapuram, India
Thiruvananthapuram, India

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Vinitha A.,Rajiv Gandhi Center for Biotechnology | Kutty V.R.,Sree Chitra Tirunal Institute for Medical Science and Technology | Vivekanand A.,Rajiv Gandhi Center for Biotechnology | Reshmi G.,Rajiv Gandhi Center for Biotechnology | And 7 more authors.
Molecular and Cellular Biochemistry | Year: 2016

Plasma level of cyclophilin A is a promising marker of vascular disease in patients with type 2 diabetes. Genetic variants in the peptidylprolyl isomerase A gene, encoding human cyclophilin may alter protein synthesis thus affecting its activity, function, and circulating plasma levels. We examined the effect of single-nucleotide polymorphisms (SNPs) within the PPIA gene on plasma levels of cyclophilin A and coupled this with status of vascular disease in patients with and without type 2 diabetes in 212 South Indian subjects. The regulatory region of PPIA gene was sequenced for SNPs. The association of SNPs with known blood markers of type 2 diabetes and coronary artery disease such as HbA1c, low- and high-density lipoproteins, triglycerides, fasting and postprandial blood sugar levels, and cyclophilin A were probed. We identified three SNPs namely, rs6850: A > G; (AG/−) c.*227_*228delAG and (−/T) c.*318_*319insT. Welchs two-sample t test indicated an association of SNP rs6850: A > G, located at the 5′ UTR region with increased plasma levels of cyclophilin A in patients with coronary artery disease and with coronary artery disease associated with diabetes. The presence of rs6850: A > G variant was significantly associated with coronary artery disease irrespective of whether the patients had diabetes or not. In silico analysis of the sequence using different tools and matrix libraries did not predict any significant differential binding sites for rs6850: A > G, c.*227_*228delAG and c.*318_*319insT. Our results indicate that the SNP rs6850: A > G is associated with increased risk for elevated plasma levels of cyclophilin A and coronary artery disease in patients with and without type 2 diabetes. © 2015, Springer Science+Business Media New York.


PubMed | Sree Chitra Tirunal Institute for Medical Science and Technology, The Madras Medical Mission, Rajiv Gandhi Center for Biotechnology, PRS Hospital and Indian Institute of Diabetes
Type: Journal Article | Journal: Molecular and cellular biochemistry | Year: 2016

Plasma level of cyclophilin A is a promising marker of vascular disease in patients with type 2 diabetes. Genetic variants in the peptidylprolyl isomerase A gene, encoding human cyclophilin may alter protein synthesis thus affecting its activity, function, and circulating plasma levels. We examined the effect of single-nucleotide polymorphisms (SNPs) within the PPIA gene on plasma levels of cyclophilin A and coupled this with status of vascular disease in patients with and without type 2 diabetes in 212 South Indian subjects. The regulatory region of PPIA gene was sequenced for SNPs. The association of SNPs with known blood markers of type 2 diabetes and coronary artery disease such as HbA1c, low- and high-density lipoproteins, triglycerides, fasting and postprandial blood sugar levels, and cyclophilin A were probed. We identified three SNPs namely, rs6850: A>G; (AG/-) c.*227_*228delAG and (-/T) c.*318_*319insT. Welchs two-sample t test indicated an association of SNP rs6850: A>G, located at the 5 UTR region with increased plasma levels of cyclophilin A in patients with coronary artery disease and with coronary artery disease associated with diabetes. The presence of rs6850: A>G variant was significantly associated with coronary artery disease irrespective of whether the patients had diabetes or not. In silico analysis of the sequence using different tools and matrix libraries did not predict any significant differential binding sites for rs6850: A>G, c.*227_*228delAG and c.*318_*319insT. Our results indicate that the SNP rs6850: A>G is associated with increased risk for elevated plasma levels of cyclophilin A and coronary artery disease in patients with and without type 2 diabetes.


Ramachandran S.,Rajiv Gandhi Center for Biotechnology | Venugopal A.,Rajiv Gandhi Center for Biotechnology | Sathisha K.,Indian Institute of Science | Reshmi G.,Cancer Research Program | And 6 more authors.
Proteomics | Year: 2012

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.


Rahim A.,Medical College Hospital | Mathew A.J.,Indian Institute of Diabetes
Journal of Postgraduate Medicine | Year: 2011

Are rheumatic musculoskeletal diseases (RMSD) given their due recognition by the medical fraternity and policy makers in India today Focus on lifestyle diseases has taken away the importance of morbidity caused by musculoskeletal pain, which is one of the commonest ailments in the community. Poor awareness in general regarding the upcoming field of rheumatology and lack of proper data regarding these diseases in the country are the primary causes for this debacle. The epidemiology of RMSD in the country is fast changing, especially in the wake of viral epidemics, which leave their mark for months and years together. This view point emphasizes the burden of RMSD by highlighting the findings of two Community Oriented Programme for the Control of Rheumatic Diseases studies conducted to study the prevalence of RMSD in rural communities in the southern state of Kerala, which inadvertently captured the burden of RMSD following Chikungunya viral epidemics in the regions. Both the studies have reported a high prevalence of RMSD following the epidemics. The value of including RMSD in a national programme to combat the morbidity caused and to improve the health related quality of life of patients has been stressed upon, in the background of altering epidemiology of these disorders in the country.


Ramachandran S.,Rajiv Gandhi Center for Biotechnology | Venugopal A.,Rajiv Gandhi Center for Biotechnology | Kutty V.R.,Sree Chitra Tirunal Institute for Medical Science and Technology | A V.,Rajiv Gandhi Center for Biotechnology | And 7 more authors.
Cardiovascular Diabetology | Year: 2014

Aims/hypothesis: Cyclophilin A, an immunophilin is secreted from human monocytes activated by high glucose. Given its role as an inflammatory mediator of vascular tissue damage associated with inflammation and oxidative stress, we examined plasma levels of cyclophilin A in normal healthy volunteers and patients with type 2 diabetes (DM), with or without coronary artery disease (CAD).Methods: Study subjects comprised of 212 patients with DM and CAD,101 patients with diabetes, 122 patients with CAD and 121 normal healthy volunteers. Diabetes was assessed by HbA1c levels while coronary artery disease was established by a positive treadmill test and/or coronary angiography. Plasma cyclophilin A was measured using a cyclophilin A ELISA Kit. Relationship of plasma cyclophilin A levels with blood markers of type 2 diabetes, blood lipid levels and medication for diabetes and coronary artery disease were also explored.Results: Plasma Cyclophilin levels were higher in diabetes patients with or without CAD compared to normal subjects (P < 0.001). Age, fasting blood sugar levels and HbA1C levels were positively associated with increased plasma cyclophilin. Patients using metformin had reduced levels of plasma cyclophilin (p < 0.001).Serum levels of total cholesterol, LDL cholesterol and triglycerides had no significant association with plasma cyclophilin levels. In patients with increased serum CRP levels, plasma cyclophilin A was also elevated (p = 0.016). Prevalence odds for DM, DM + CAD and CAD are higher in those with high cyclophilin values, compared to those with lower values, after adjusting for age and sex, indicating strong association of high cyclophilin values with diabetes and vascular disease.Conclusions/interpretations: Our study demonstrates that patients with type 2 diabetes have higher circulating levels of cyclophilin A than the normal population. Plasma cyclophilin levels were increased in patients with diabetes and coronary artery disease suggesting a role of this protein in accelerating vascular disease in type 2 diabetes. Considering the evidence that Cyclophilin A is an inflammatory mediator in atherogenesis, the mechanistic role of cyclophilin A in diabetic vascular disease progression deserves detailed investigation. © 2014 Ramachandran et al.; licensee BioMed Central Ltd.

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