Association of albumin, fibrinogen, and modified proteins with acute coronary syndrome.

Acute coronary syndrome (ACS) comprises a pathophysiological spectrum of cardiovascular diseases related to atherosclerotic coronary plaque erosion. Oxidative stress and inflammation play pivotal roles in the development and progression of atherosclerosis, which affects circulatory proteins, including albumin and fibrinogen, thereby causing an imbalance in albumin to globulin and fibrinogen to albumin ratios. This study aimed to assess the effect of oxidative stress on circulatory proteins, correlate these parameters, and investigate their significance in patients with ACS. In this case-control study, the major blood proteins in patients with ACS and a control group were evaluated using standard methods. Out of 70 ACS cases, 75.7% had ST-elevation myocardial infarction (STEMI), 18.6% had non-STEMI, and 5.7% had unstable angina. The mean cardiac troponin I level in patients was 12.42 ng/mL. The patients demonstrated a significantly reduced level of human serum albumin (HSA), 3.81 ± 0.99 g/dL, compared to controls, 5.33 ± 0.66 g/dL. The albumin to globulin ratio (AGR) was significantly depressed in patients while their mean fibrinogen level and the fibrinogen to albumin ratio (FAR) were significantly higher. Multivariate logistic regression analysis showed that albumin and fibrinogen were significantly associated with the risk of ACS, showing the potential of these parameters to be used for risk assessment of ACS. The ischemia modified albumin (IMA) and protein carbonyls were significantly higher in patients which showed significant positive correlations with FAR. Albumin, IMA and protein carbonyls were found to have high diagnostic sensitivity and specificity for ACS. Overall, these circulatory and modified proteins in ACS patients, particularly lower HSA, AGR, and higher IMA and protein carbonyls may help assess risk.

A computational in silico approach to predict high-risk coding and non-coding SNPs of human PLCG1 gene.

PLCG1 gene is responsible for many T-cell lymphoma subtypes, including peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma (AITL), cutaneous T-cell lymphoma (CTCL), adult T-cell leukemia/lymphoma along with other diseases. Missense mutations of this gene have already been found in patients of CTCL and AITL. The non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein structure as well as its functions. In this study, probable deleterious and disease-related nsSNPs in PLCG1 were identified using SIFT, PROVEAN, PolyPhen-2, PhD-SNP, Pmut, and SNPS&GO tools. Further, their effect on protein stability was checked along with conservation and solvent accessibility analysis by I-mutant 2.0, MUpro, Consurf, and Netsurf 2.0 server. Some SNPs were finalized for structural analysis with PyMol and BIOVIA discovery studio visualizer. Out of the 16 nsSNPs which were found to be deleterious, ten nsSNPs had an effect on protein stability, and six mutations (L411P, R355C, G493D, R1158H, A401V and L455F) were predicted to be highly conserved. Among the six highly conserved mutations, four nsSNPs (R355C, A401V, L411P and L455F) were part of the catalytic domain. L411P, L455F and G493D made significant structural change in the protein structure. Two mutations-Y210C and R1158H had post-translational modification. In the 5' and 3' untranslated region, three SNPs, rs139043247, rs543804707, and rs62621919 showed possible miRNA target sites and DNA binding sites. This in silico analysis has provided a structured dataset of PLCG1 gene for further in vivo researches. With the limitation of computational study, it can still prove to be an asset for the identification and treatment of multiple diseases associated with the target gene.