Correlation Between Estrogen Receptor α Gene Polymorphism (c454-397T>C) with Serum Estradiol Levels and Known Risk Factors in Patients with Myocardial Infarction.

Myocardial infarction (MI) remains the most common cause of cardiac failure and continuous increasing rate of morbidity and mortality. We aimed to investigate the association of estrogen receptor-α (ESR1) gene polymorphism c454-397T>C with serum estradiol levels and dyslipidemia in 220 patients with MI in the age range of 35-70 years of both the genders. Genotyping study was performed through PCR-RFLP method using PvuII restriction enzyme. Serum estradiol level was estimated using the Access Sensitive Estradiol assay kit. Men patients had 43.2% increased risk for TC heterozygote in co-dominant (OR 10.66) and over-dominant models (OR 8.30), while women patients had 50% increased risk in co-dominant (OR 16.57) and over-dominant (OR 14.04) models. Variant C allele showed 25% increased risk of MI for in men (OR 2.24; CI 1.49-3.36; p = 0.0001), and 24% increased risk in women (OR 3.35; CI 1.95-5.76; p = 0.0001). Men patients had significantly increased serum estradiol levels compared to controls (25.28 ± 5.80 vs 17.04 ± 2.01; p < 0.0001). Significant difference was observed in estradiol levels between men and women patients (25.28 ± 5.80 vs 17.56 ± 3.32; p < 0.0001). Furthermore, significantly increased estradiol level was found in men patients compared to women for TT (25.46 ± 5.91 vs 16.71 ± 4.46; p < 0.0001), and TC genotypes (25.47 ± 5.91 vs 17.70 ± 2.86; p < 0.0001). Significantly increased HDL levels were observed in men patients with TC (43.10 ± 8.18 vs 38.91 ± 7.84; p < 0.01) and CC (47.16 ± 8.09 vs 38.91 ± 7.84; p < 0.001) genotypes compared to TT genotype. These findings suggest that TC heterozygote plays an important role as a genetic risk factor during MI pathogenesis in the South Indian population. Supplementary Information: The online version contains supplementary material available at 10.1007/s12291-022-01104-1.

Association of Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism with Angiotensin II Serum Levels in Patients with Essential Hypertension.

Essential hypertension (EH) is a multifactorial, polygenic condition, and is one of the most important comorbidities that contributes to stroke, myocardial infarction, cardiac failure, and renal failure. The continuous increasing rate of morbidity and mortality associated with EH presents an unmet need of population-based studies to explore pathophysiology as well as newer strategies for better diagnosis, prognosis and treatment. This study aimed to determine genotype and allele frequencies of A1166C polymorphism of AT1R gene in Indian patients with EH and correlated with serum levels of Angiotensin II. A total of 200 patients with EH and 200 age- and gender-matched control individuals were included in this study from the General Medicine Department Outpatient at Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India. Patients with systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg were considered as hypertensive. The findings of this study revealed significantly increased risk of C/A heterozygote and allele C in both men and women. Moreover, both men and women patients with EH showed higher serum levels of Angiotensin II with C/A as well as AA genotypes. These findings indicate a significant association of 1166 C/A polymorphism of the AT1R gene with increased risk of hypertension in Indian population.

Simultaneous extraction and quantification of circulating mitochondrial and nuclear DNA using a single plasma sample to predict specific molecular diagnostic implications.

The magnitude of variations in the level of circulating mitochondrial (cir-mtDNA) and nuclear DNA (cir-ncDNA) in different diseases has indicated the need for investigating a discriminative approach for evaluating their diagnostic significance. This study reports a typical in-house process for extracting both types of cir-DNAs from a single plasma sample and assessed their usefulness in discriminating type 2 diabetes mellitus patients from healthy individuals to eliminate the prevailing dispute about their discriminative role and improve their diagnostic value. This approach offers a more precise and valuable tool for distinguishing the impact of cir-mtDNA from cir-ncDNA in diagnostic implications.

Status of Vitamin D Receptor Gene Polymorphism and 25-Hydroxy Vitamin D Deficiency with Essential Hypertension.

Essential hypertension (EH) is a multifactorial and complex disease with high rate of incidence and associated co-morbidities. Previous studies do not provide unanimous results for the risk of hypertension and association with Fok I genotype frequency and serum vitamin D levels. Hence, this study was undertaken to determine the status of Fok I vitamin D receptor (VDR) gene polymorphism along with vitamin D levels and blood pressure in patients with EH. Four hundred (200 controls and 200 cases of essential hypertension) participants from general Indian population were enrolled in this study. Peripheral blood samples were collected for genotyping Fok I-VDR gene polymorphism using PCR-RFLP method whereas 25-OH vitamin D levels in serum were quantified using high performance liquid chromatography (HPLC). Significantly reduced 25-OH vitamin D levels were observed in patients with EH (24.04 ± 8.62 vs 50.46 ± 15.46) compared to control subjects (p = 0.0001). Homozygous recessive genotype 'ff' frequency was increased by 8.06 fold (CI: 3.71-17.47, p = 0.0001) in patients with EH compared to dominant 'FF' genotype frequency. In conclusion, recessive 'ff' genotype frequency correlates with reduced serum vitamin D levels and results in significantly increased systolic and diastolic blood pressures leading to predisposition of EH.

Association and gene-gene interaction analyses for polymorphic variants in CTLA-4 and FOXP3 genes: role in susceptibility to autoimmune thyroid disease.

PURPOSE: Polymorphic variants of cytotoxic T-lymphocyte antigen-4 (CTLA-4) and forkhead box protein P3 (FOXP3) genes are implicated in dysregulated immune homeostasis and autoimmune disorders. We analyzed the association between CTLA-4 rs231775 and FOXP3 rs3761548, rs3761549 polymorphisms and predisposition to autoimmune thyroid disease (AITD), inclusive of Hashimoto's thyroiditis (HT) and Graves' disease (GD) in South-Indian population. METHODS: A total of 355 AITD subjects (comprising 275 HT and 80 GD) and 285 randomly selected age- and sex-matched control subjects were genotyped for the aforementioned polymorphisms by PCR-RFLP method. RESULTS: The rs231775 "G" allele was preponderant in HT and GD subjects when compared with controls and exerted a dominant influence on the susceptibility to HT (p = 0.009) and GD (p = 0.02), respectively. There was no allelic association of rs3761548 and rs3761549 polymorphisms with AITD susceptibility, albeit a significant difference in genotype distribution with respect to rs3761549. Haplotype analysis revealed an increased frequency of rs3761548 "C"-rs3761549 "T" in HT and GD subjects, thereby associating it with disease predisposition (p = 0.03). Epistatic interaction analysis by multifactor dimensionality reduction approach revealed redundancy between CTLA-4 and FOXP3 genes in influencing the susceptibility to AITD. CONCLUSIONS: The genetic variation in CTLA-4 gene with reference to rs231775 polymorphism contributes to an increased predisposition to HT and GD. Also, in conjunction with FOXP3 gene variants it seems to influence the susceptibility to HT and GD respectively. The significance of these findings in combination with antithyroid antibody screening could plausibly contribute towards meticulous case-finding for effective treatment of HT and GD.

Protective Role of Hypothermia Against Heat Stress in Differentiated and Undifferentiated Human Neural Precursor Cells: A Differential Approach for the Treatment of Traumatic Brain Injury.

INTRODUCTION: The present study aimed to explore protective mechanisms of hypothermia against mild cold and heat stress on highly proliferative homogeneous human Neural Precursor Cells (NPCs) derived from Subventricular Zone (SVZ) of human fetal brain. METHODS: CD133+ve enriched undifferentiated and differentiated human NPCs were exposed to heat stress at 42°C. Then, Western-blot quantification was performed using Hsp-70 (70 kilodalton heat shock proteins) recombinant protein. Finally, changes in pluripotency and Hsp-70 expression were measured using immunofluorescence staining and RT-qPCR (Quantitative reverse transcription PCR) analysis, respectively. RESULTS: Heat stress resulted in abnormal neurospheres development. The apoptosis rate was enhanced during long-term in vitro culture of neurospheres. Neurogenic differentiation reduced and showed aberrent phenotypes during heat stress. After hypothermia treatment significant improvement in neurospheres and neuronal cell morphology was observed. CONCLUSION: Mild-hypothermia treatment induces attenuated heat shock response against heat stress resulting in induced HSP-70 expression that significantly improves structure and function of both undifferentiated human NPCs and differentiated neurons.

Management of chronic allograft dysfunction by switch over to rapamycin.

The aim of this study was to evaluate the efficacy of conversion from calcineurin inhibitors (CNI)-based to a rapamycin-based immunosuppressive regimen in renal transplant recipients who had allograft dysfunction, in a South Indian population. We analyzed the results of 75 (19.5%) of the 398 renal transplants performed over a five-year period from 2002 to 2007, who were converted from a CNI-based immunosuppression to rapamycin including patients with chronic allograft dysfunction, chronic allograft injury and malignancy. The data analyzed included serial rapamycin levels, serum creatinine, eGFR by nankivel formula, lipid profile, hemoglobin and serum potassium levels. Statistical analysis was performed using student's t test and the Kaplan Meir survival curve was used to predict probability of survival among patients on rapamycin. The mean age of the study patients was 39.6 + or - 12.2 yrs and there was a male predominance (74.6%). Diabetic nephropathy was the predominant cause (36%) of end-stage renal disease (ESRD). Statistical analysis revealed a significant improvement in GFR of 14.6 mL/min and decrease in potassium by 0.7 mmol/L after initiation of rapamycin. There were no significant differences in terms of lipid profile, platelet count, hemoglobin and urine albumin levels. Rapamycin was discontinued in one patient due to hypokalemic nephropathy and in another patient due to delayed wound healing. To our knowledge, this is the first study to provide information on the conversion from a CNI to rapamycin-based immunosuppression in a cohort of Indian renal transplant recipients. In conclusion, the findings of our study confirm that rapamycin-based immunosuppressive regimen improves renal function and graft survival with minimal side effects, in comparison to CNI-based immunosuppression.

Can serial eGFR, body mass index and smoking predict renal allograft survival in south Asian patients.

Limited data exist regarding long-term allograft survival in South Asian patients in the era of modern immunosuppressive therapy. This retrospective cohort study was undertaken to see the graft survival based on serial eGFR, immunosuppressive therapy, BMI and other confounding factors including smoking in patients who have undergone renal transplantation in a tertiary care center in south India. Three hundred and three kidney transplant recipients including live and cadaveric transplantation performed between 2001 and 2006 were included in this study. The mean graft survival after transplantation was 6.38 +/- 0.11 years, graft survival at one, two, three and five years were 95.7%, 92.72%, 91.72% and 89.21%, respectively. The mean serum creatinine and eGFR in the biopsy proven acute rejection (BPAR) group were 1.74 +/- 0.94 mg/dL and 43.73 +/- 13.65 mL/min com-pared with 1.24 +/- 0.59 mg/ dL and 61.50 +/- 17.40 mL/min in the non-BPAR group (P < 0.001 and P= 0.0159) respectively. The mean BMI in the BPAR group at one year was 26.59 +/- 3.18 kg/m 2 compared with 21.63 +/- 2.29 kg/m 2 in the non-BPAR group (P < 0.05). The mean graft survival in patients who were smokers at the time of pretransplant evaluation was 89.3% compared with 92.5% in the non-smokers (P=0.347). This retrospective cohort study found that serial eGFR, body mass index and smoking were significant predictors of graft survival following renal transplantation in South Asian patients.