Folate Pathway Gene Methylenetetrahydrofolate Reductase C677T Polymorphism and Alzheimer Disease Risk in Asian Population

The association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and susceptibility to Alzheimers disease (AD) was controversial in previous studies. The present meta-analysis was designed to investigate the association of MTHFR C677T polymorphism with AD. Nine studies were identified by search of PubMed, Google Scholar, Elsevier, Springer Link databases, up to January 2013. Odds ratios (ORs) with corresponding 95 % confidence interval (CI) were calculated using fixed effects model or random effects model. All statistical analysis was done by Mix version 1.7. MTHFR C677T polymorphism had a significant association with susceptibility to AD in all genetic models (for T vs C: OR 1.29, 95 % CI 1.15–1.44, p < 0.0001; for TT + CT vs CC: OR 1.38, 95 % CI 1.16–1.364, p = 0.0002; for TT vs CC: OR 1.60, 95 % CI 1.25–2.04, p = 0.0001; for CT vs CC: OR 1.28, 95 % CI 1.1–1.53, p < 0.008; for TT vs CT + CC: OR 1.37, 95 % CI 1.12–1.67, p = 0.002). Results from present meta-analysis supported that the MTHFR C677T polymorphism was associated with an increased risk of AD in Asian population.     

Strong Association of C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene With Nosyndromic Cleft Lip/Palate (nsCL/P)

Methylenetetrahydrofolate reductase (MTHFR) is essential for DNA biosynthesis and the epigentic process of DNA methylation. It has been reported that abnormal DNA methylation contributes to the pathogenesis of congenital anomalies. There were many published case control studies assessing the associations of MTHFR C677T polymorphism with risks of nosyndromic cleft lip with and without palate (nsCL/P), but with inconsistent results. To derive a more precise estimation of the relationship, a meta-analysis was performed. Eligible articles were identified by search of databases including PubMed, Science Direct, Google Scholar and Springer Link up to December, 2015. Finally, a total of 22 studies with 3724 nsCL/P cases and 5275 controls were included in the present meta-analysis. Odds ratios (ORs) with corresponding 95% confidence intervals (95% CIs) were pooled to assess the association. Subgroup analysis based on ethnicity was also performed. All statistical analyses were done by MIX program. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased nsCL/P risk in overall population using four genetic models except homozygote model (for T vs. C: OR = 1.24, 95% CI = 1.1–1.4; for TT + CT vs. CC: OR = 1.29, 95% CI = 1.04–1.59; for CT vs. CC: OR = 1.26, 95% CI = 0.98–1.63; for TT vs. CC: OR = 1.02, 95% CI = 0.74–1.4; for TT vs. CT + CC: OR = 1.36, 95% CI = 1.05–1.74). In conclusion, results of present meta-analysis suggested that MTHFR C677T polymorphism is significantly associated with nonsyndromic orofacial cleft.     

Methylenetetrahydrofolate Reductase C677T Polymorphism and Recurrent Pregnancy Loss Risk in Asian Population: A Meta-analysis

The C677T polymorphism of the methylenetetrahydrofolate reductase (MTHFR) gene was implicated to be associated with thrombophilia due to its role in catalyzing the formation of 5-methylenetetrahydrofolate, a co-substrate for the conversion of homocysteine to methionine. Several case–control studies were investigated MTHFR C677T polymorphism as risk for recurrent pregnancy loss (RPL). These studies rendered contradictory results, some indicating that the polymorphism is associated with the risk of RPL whereas others concluded there is no association. To shed light on these inconclusive findings, a meta-analysis of all available studies published from Asian population relating the C677T polymorphism to the risk of RPL was conducted. The following electronic databases were searched without language restrictions: PubMed, Google Scholars, Elsevier and Springer Link up to December, 2015. Meta-analysis was performed using MetaAnalyst and Mix version 1.7. Meta-analysis results suggested that MTHFR C677T polymorphism contributed to the increased RPL risk in Asian population using all five genetic models (for T vs. C: OR 1.35, 95 % CI 1.09–1.68, p = 0.009; for TT + CT vs. CC: OR 1.44, 95 % CI 1.14–1.82, p = 0.006; for CT vs. CC: OR 1.39, 95 % CI 1.07–1.8, p = 0.01; for TT vs. CC: OR 1.79, 95 % CI 1.23.2.6, p = 0.007; for TT vs. CT + CC: OR 1.61, 95 % CI 1.02–2.56, p = 0.04). In conclusion, this meta-analysis demonstrates a strong association between the MTHFR C677T variant and RPL in Asian population and raising the importance of the use of folate in its treatment and prevention.     

Genetic Variant XRCC1 rs1799782 (C194T) and Risk of Cancer Susceptibility in Indian Population: A Meta-analysis of Case–Control Studies

X-ray repair cross-complementing group 1 (XRCC1) plays a key role in the base excision repair pathway, as a scaffold protein that brings together proteins of the DNA repair complex. Several studies have reported contradictory results for XRCC1 exon 6 C>T (rs1799782) gene polymorphism and cancer risk in Indian population has provided inconsistent results. Therefore, we have performed this meta-analysis to evaluate the relationship between XRCC1 exon 6 C>T gene polymorphism and risk of cancer by published studies. We searched PubMed and Google scholar web databases to cover all studies published on association between XRCC1 exon 6 C>T gene polymorphism and cancer risk. The meta-analysis was carried out and pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. In order to derive a more precise estimation of the association, A total of 3197 confirmed cancer cases and 3819 controls were included from eligible seventeen case-controls studies. Results from overall pooled analysis demonstrated suggested that that variant allele (T vs. C: OR 1.301, 95% CI 1.003–1.688, p = 0.047) was associated with the risk of overall cancer. Other genetic models; heterozygous (TC vs. CC: OR 1.108, 95% CI 0.827–1.485, p = 0.491), homozygous (TT vs. CC: OR 1.479, 95% CI 0.877–2.493, p = 0.142), dominant (TT+TC vs. CC: OR 1.228, 95% CI 0.899–1.677, p = 0.196) and recessive (TT vs. TC+CC: OR 1.436, 95% CI 0.970–2.125, p = 0.071) did not reveal statistical association. Publication bias observation was also considered and none was detected during the analysis. The present meta-analysis suggested that the variant allele T of XRCC1 exon 6 gene polymorphism was associated with the risk of cancer. It is therefore pertinent to confirm this finding in a large sample size to divulge the mechanism of this polymorphism and cancer risk in Indian population.     

Genetic Variant Arg399Gln G&gt;A of XRCC1 DNA Repair Gene Enhanced Cancer Risk Among Indian Population: Evidence from Meta-analysis and Trial Sequence Analyses

The X-ray repair cross-complementation group 1 (XRCC1) gene plays an important role in base excision repair pathway. Several studies have reported contradictory results for XRCC1 exon 10 (Arg399Gln, G23990A, rs25487) gene polymorphism and cancer risk in Indian population, making it difficult to interpret them. Therefore, we have conducted a meta-analysis to evaluate the more precise association between XRCC1 exon 10 G>A gene polymorphism and risk of cancer by published studies. We searched PubMed (Medline) and Google scholar web databases to cover all studies published on association between XRCC1 exon 10 G>A gene polymorphism and cancer risk until August 2016. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to appraise the strength of association. Heterogeneity, publication bias and sensitivity analysis were also assessed. Twenty-five published studies had fulfilled the inclusion criteria comprising 4131 confirmed cancer cases and 5013 controls. When all studies were polled together, overall significant association was found between XRCC1 exon 10 G>A polymorphism and cancer risk in variant allele carrier (A vs. G: OR 1.217, 95% CI 1.056–1.402, p = 0.007), homozygous (AA vs. GG: OR 1.359, 95% CI 1.036–1.783, p = 0.027), dominant (AA+AG vs. GG OR 1.208, 95% CI 1.006–1.450, p = 0.043) and recessive (AA vs. AG+GG: OR 1.315, 95% CI 1.029–1.680, p = 0.029) genetic models. Further sensitivity analysis supported the stability of our result by showing similar ORs before and after removal of a single study. The present meta-analysis suggested that the XRCC1 exon 10 G>A polymorphism contribute cancer risk in Indian population, and supports that individuals with risk allele A and AA genotype are at higher risk of developing cancer.     

MTHFR (Ala 222 Val) polymorphism and AMI in patients with type II diabetes mellitus

The prevalent Ala222Val single nucleotide polymorphism of the MTHFR gene has been shown to be associated with type II diabetes. The objective of the present study was to find out whether there is genetic predisposition for development of acute myocardial infarction in type II diabetes mellitus among South Indian Tamil population. PCR-based restriction enzyme analysis was performed in DNA isolated from 120 acute myocardial infarction patients with diabetes mellitus and 100 non diabetic healthy individuals with no documented cardiovascular diseases. The results indicate that the MTHFR 677TT genotype is absent in both case and controls. The MTHFR 677CT genotype was observed among 32 (26.7 %) cases and 20 (20%) controls and the MTHFR 677CC genotype among 88 (73.3%) cases and 80 (80%) controls. The allelic frequencies were in accordance to Hardy Weinberg equilibrium. There was no statistical difference in genotype distribution between cases and controls. In conclusion, we suggest that the analysis of MTHFR genotyping for C677T polymorphism alone need not be considered to find out whether there is genetic predisposition for development of acute myocardial infarction in type II diabetes mellitus among South Indian Tamil population.     

Polymorphism (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene: A preliminary study on north Indian men

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B₁₂, B₆ can lead to hyperhomocysteinemia. In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher ‘T’ allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.     

Cytochrome P450 Genes (CYP2E1 and CYP1A1) Variants and Susceptibility to Chronic Hepatitis B Virus Infection

Hepatitis B virus (HBV) infection is a worldwide health concern which is associated with significant morbidity and mortality. Both viral and host factors have a significant effect on infection, replication and pathogenesis of HBV. The aim of this study was to investigate the effect of CYP2E1 and CYP1A1 genetic variants on susceptibility to HBV. 143 individuals including 54 chronic HBV patients and 89 healthy controls were enrolled in the genotyping procedure. rs2031920 and rs3813867 at CYP2E1 as well as rs4646421 and rs2198843 at CYP1A1 loci were studied in all subjects using PCR–RFLP (restriction fragment length polymorphism) analysis. Both variants at CYP2E1 locus were monomorphic in all studied subjects. Genotype frequency of rs4646421 was significantly different between chronic HBV patients and healthy blood donors (P = 0.04, OR 4.31; 95% CI 1.04–17.7). Furthermore, individuals carrying at least one C allele (CC or CT genotypes) for rs4646421 seemed to have a decrease risk of hepatitis in comparison with TT genotype (P = 0.039). Our results showed a relationship between rs4646421 TT genotype (rare genotype) and the risk for developing chronic HBV infection (four times higher). Further studies are needed to examine the role of CYP1A1 polymorphism in susceptibility to chronic HBV infection.     

Pre-micro RNA-499 Gene Polymorphism rs3746444 T/C is Associated with Susceptibility to Rheumatoid Arthritis in Egyptian Population

Pre-miRNA-499 gene is associated with autoimmune disease. Mir-449 rs3746444 polymorphism is inconsistent for rheumatoid arthritis (RA). This study aimed to investigate association of mir-499 rs3746444 polymorphism with RA activity and severity in Egyptian population. The study population was conducted as case control study in 100 RA patients diagnosed according to the American College of Rheumatology classification criteria for RA, and the control group included 100 healthy subjects who were age-and sex-matched to the RA group. Different genotypes were assessed using polymerase chain reaction–restriction fragment length polymorphism. 95% Confidence interval and odds ratio were defined to assess the strength of association. Regarding patients, thirty-three patients carried TT genotype, fifty-three patients carried TC genotype and fourteen patients carried CC genotype. So the frequency of the minor C allele in RA patients was significantly higher than the control subjects (P = 0.037). TC, CC genotypes and C allele frequencies were significantly associated with disease severity as they had high rheumatoid factor (55.78 µIU/ml) and anti-cyclic citrullinated peptide (Anti-CCP) antibody (297.32 µIU/ml). Moreover, the heterozygote TC had more severe and more active form of the disease compared with homozygote CC or TT as they had high Anti-CCP antibody, and disease activity score 28 (score 5). Our work suggests that C allele of Pre-miRNA rs3746444 polymorphism contributes to heritability of susceptibility to RA compared to T allele. This polymorphism was associated with the activity and severity of the disease.     

C677T MTHFR Gene Polymorphism is Contributing Factor in Development of Renal Impairment in Young Hypertensive Patients

Homocysteine concentration affected by the activities of the enzymes methylene tetra-hyrdofolate reductase (MTHFR). Polymorphisms in MTHFR gene associated with an impairment of MTHFR activity. Hyperhomocysteinemia is a result of single nucleotide polymorphisms (SNPs) in MTHFR 677 C>T that can cause homocysteine levels in the blood to increase. The purpose of this study is to investigate the relationships between MTHFR C677T (rs1801133) gene polymorphism, changes in homocysteine concentrations and progress of renal impairment in young adult hypertensive patients. Two hundred young hypertensive patients (age 21–24 years) were involved in this study; they were classified into patients with and without renal impairment in addition to 200 age and sex matched healthy controls. All participants were submitted to laboratory investigations as assay of MTHFR gene polymorphism C677T (rs1801133) by PCR/RFLP, determination of lipid profile, homocysteine and folic acid concentrations in addition to urinary albumin creatinine ratio (UACR). The levels of both homocysteine and UACR in the TT genotype patients were higher than those in the CC genotype group. Individuals who carry the T allele were more risky to hypertension and progress to early renal impairment in young age compared with those carrying the C allele [OR 2.02 (1.33–3.08), P < 0.001]. Genetic variants of C677T MTHFR gene and hyperhomocysteinemia may be responsible for rapid progress of renal impairment in Egyptian young age hypertensive patients. TT genotype or T allele may be considered as a predisposing factor for both elevated Hcy levels and the development of renal impairment. This study believed that lowering of homocysteine level can reduce renal impairment of hypertensive patients.     

A Synergistic Role of Myeloperoxidase and High Sensitivity Troponin T in the Early Diagnosis of Acute Coronary Syndrome

Aim of this study was to evaluate the role of Myeloperoxidase (MPO) and high sensitive Troponin T in the early diagnosis of acute coronary syndrome (ACS). This was a cross sectional study that comprised of 120 individuals of which 75 were cases and 45 healthy controls. On the basis of clinical history and 12 lead electrocardiogram initial diagnosis of ACS was made in the cases. MPO and high sensitive Troponin T (hs-cTnT) was measured in all the individuals. Levels of MPO were significantly higher in patients of ACS as compared to those in control group [medians: 15.40 (95 % CI 11.06–20.84) vs 5.84 (95 % CI 5.50–6.44)]. By taking the cut off as >11.87 U/mL for MPO, its sensitivity was 87 % (95 % CI 73.7–95.1), specificity was 97.3 % (95 % CI 90.6–99.7), positive predictive value was 94.6 % and negative predictive value was 92.6 %. Positive likelihood ratio was 33.0 while negative likelihood ratio was 0.13, whereas the corresponding values in case of hs-cTnT were 95.6 % (95 % CI 85.2–99.5), 61.3 % (95 % CI 49.5–72.6), 59.7 %, 95.8 %, 2.47 and 0.07 by taking cut off as >14 pg/ml. The area under the ROC curves (AUC) of MPO and hscTnT at 0–6 h were 0.971 (95 % CI 0.92–0.99, P < 0.001) and 0.797 (95 % CI 0.71–0.86, P < 0.001) respectively. The logistic model combining the two markers yielded sensitivity, specificity, positive predictive value and negative predictive value of 95.7, 97.3, 98.2 and 93.7 % respectively. It was concluded that MPO and hs-cTnT may be useful tools for risk stratification of ACS and can be used together with better accuracy in the early diagnosis of ACS.     

Association of Aberrations in One Carbon Metabolism with Intimal Medial Thickening in Patients with Type 2 Diabetes Mellitus

The present work was aimed to study the association of one carbon genetic variants, hyperhomocysteinemia and oxidative stress markers, i.e., serum nitrite, plasma malondialdehyde (MDA) and glutathione (GSH) on intimal medial thickening (IMT) in patients with type 2 diabetes mellitus (T2D). A total number of 76 subjects from ACS Medical College and Hospital, Chennai, India were included in the study, i.e., Group I (n = 42) of T2D and Group II (n = 34) of age- and sex matched healthy controls. The glycated haemoglobin was measured by ion-exchange resin method; plasma homocysteine by Enzyme Linked Immunosorbant Assay method; serum nitrite (nitric oxide, NO), plasma MDA and GSH by spectrophotometric methods; the IMT by high frequency ultrasound. The polymorphisms of one carbon genetic variants were genotyped using polymerase chain reaction-restriction fragment length polymorphism and amplified fragment length polymorphism methods. Results indicate that methyltetrahydrofolate homocysteine methyl transferase (MTR) A2756G allele was found to be protective in T2D and the other variants were not significantly associated with T2D. Glutamate carboxypeptidase II (GCP II) C1561T (r = 0.34; p = 0.05) and methylene tetrahydrofolate reductase (MTHFR) C677T (r = 0.35; 0.04) showed positive correlation with plasma homocysteine in T2D cases. In this study, MTR A2756G allele was found to be protective in T2D; GCP II C1561T and MTHFR C677T showed positive association with plasma homocysteine in T2D cases. Among all the genetic variants, MTR A2756G was found influence IMT. RFC 1 G80A and TYMS 5′-UTR 2R3R showed synergistically interact with MTR A2756G in influencing increase in IMT.     

Implications of ACE (I/D) Gene Variants to the Genetic Susceptibility of Coronary Artery Disease in Asian Indians

Angiotensin-1-converting enzyme (ACE) gene has established substantial attention in the recent years as a candidate gene for hypertension, cardiovascular diseases and type 2 diabetes. The aim of the present study was to investigate the association of ACE (I/D) polymorphism with coronary artery disease (CAD) in a north Indian population. A total of 662 subjects (330 CAD patients and 332 healthy controls) were examined for association of ACE gene (I/D) polymorphism and environmental risk factors. The mean age of the CAD patients and control subjects was 60.53 ± 8.6 years and 56.55 ± 7.7 years, respectively (p = 0.000). Anthropometric and demographic data showed BMI values significantly higher among CAD patients and control subjects (26.98 ± 4.9 vs 24.04 ± 4.7, p = 0.000). We observed pronounced central obesity in both CAD patients and controls, even at the lowest BMI values (<23 kg/m²). Dyslipidemia was highly prevalent in CAD patients compared to control subjects. Genotypic data showed significantly higher frequency of DD genotype in CAD patients than that of control subjects (40 vs 28.3 %). No significant difference was observed in the distribution of ID genotypes between CAD patients and control subjects. Logistic regression analysis of data demonstrate that DD genotype was associated with 1.8 fold increased risk of development of CAD in Asian Indians (OR 1.8; 95 % CI 1.22–2.66; p = 0.003). The frequency of D allele was significantly higher in CAD patients (p = 0.001). No significant difference was observed in the clinical and biochemical characteristics of CAD patients and controls when the data was stratified according to the genotypes of ACE gene. In conclusion, DD genotype of ACE gene may be associated with increased risk of CAD in Asian Indian population.     

Prevalence of Factor V Leiden-G1691A and MTHFR-C677T Thrombosis Gene Modifier in Iron Deficiency Anemia: A Pathophysiological Effect in Indian Isolates

Normal iron levels are required to prevent thrombocytosis by inhibiting thrombopoiesis. Thrombocytosis is usually associated with a mild iron deficiency and is the result of a lack of inhibition of thrombopoiesis. Study participants were 430 iron deficiency anemia (IDA) patients. Ten (10) mL of venous blood were collected for the subjects. Ferritin analysis was done by ELISA method while Hemogram analysis was done by auto-analyzer. Factor V Leiden, PRTG20210A, and MTHFR C677T genotype analysis was performed by PCR–RFLP method. Among the patients, 9 were heterozygous (G>A) and 2 were homozygous (A>A) carrier of FV Leiden; while 20 were heterozygous (C>T) and 3 were homozygous (T>T) for MTHFR polymorphism. None of the patient was identified with PT mutation. Patients with thrombosis gene marker had lower hemoglobin, mean corpuscular volume, mean corpuscular haemoglobin levels, and mean corpuscular hemoglobin concentration than patients without thrombosis gene marker. Serum ferritin was elevated in subject with the absence of thrombosis gene markers. Our data suggest a high impact of inherited hypercoagulability risk factors in the pathogenesis of IDA and its complications.     

Investigation of ABCA1 C69T polymorphism in patients with type 2 diabetes mellitus

Introduction:

Non insulin dependent diabetes mellitus is the most common type of diabetes. Genetic factors, lipid profiles, hypertension are potential risk factors for diabetes mellitus. Adenosine binding cassette transporter proteins 1 (ABCA1) plays a role in cholesterol metabolism, especially high density lipoprotein (HDL-cholesterol). There are multiple mechanisms by which HDL-cholesterol can be atheroprotective, it is clear that the relative activity of ABCA1 plays a major role. We aimed to investigate association of ABCA1 C69T gene polymorphism with lipid levels in Turkish type 2 diabetic patients.

Materials and methods:

After isolation of DNA by ethanol precipitation we determined ABCA1 gene polymorphism by using polimerase chain reaction - restriction fragment lenght polymorphism (PCR-RFLP) method in 107 type 2 diabetic patients and 50 healthy controls.

Results:

We have observed that the frequency of TT genotype is significantly higher in healthy controls compared to patients (14% vs. 3%; P = 0.008). Also frequency of T allele was higher in controls than in patients (34% vs. 21%; P = 0.020; OR (95% CI) = 0.52 (0.30–0.88)). There was no association of lipid levels and ABCA1 C69T polymorphism subgroups.

Conclusion:

We have found significantly higher frequency of both T allele and genotype in control group when compared to patients that made us think that T allele may be a protective factor against diabetes mellitus. But, we could not find a relationship between genotypes and lipid concentrations in our two groups. Larger studies will help us to understand the relationship between ABCA1 C69T genotype and lipid parameters in diabetes mellitus.     

Association of CETP and LIPC Gene Polymorphisms with HDL and LDL Sub-fraction Levels in a Group of Indian Subjects: A Cross-Sectional Study

There is an increasing interest to understand the molecular basis of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) subfractions and their association with coronary artery disease (CAD). The formation of these subfractions is greatly influenced by hepatic lipase (HL) and cholesteryl ester transfer protein (CETP) enzymes. To identify genetic markers influencing LDL and HDL subfractions and their role in CAD we performed a case–control genetic association study on 117 healthy controls and 119 angiographically verified CAD patients. Biochemical analysis was performed using standard assays. HDL-C and LDL-C subfractions were estimated using precipitation methods. Genotyping of C-514T (rs1800588) in the LIPC gene for HL and I405V (rs5882) in the CETP gene was done using PCR-based restriction enzyme analysis and sequencing. Both the polymorphisms were not associated with CAD. The C-514T was associated with increased HDL₃-C levels in controls (P = 0.049). The I405V polymorphism was found to be associated with low levels of small dense, LDL (P = 0.038). A multiple regression analysis showed that the effects were dependent on gender and triglyceride levels. We conclude that these polymorphisms are not associated with CAD but are important determinants of HDL-C and small dense LDL particles in our population.     

Soluble Tumor Necrosis Factor Like Weak Inducer of Apoptosis and Vitamin D in Hemodialysis Patients: Relation to Carotid Intima-Media Thickness

Cardiovascular disease, as the leading cause of patient death with chronic kidney disease, could be predicted by carotid atherosclerosis. The aim of the present study was to evaluate a possible relationship between serum soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and Vitamin D levels with mean right/left carotid intima-media thickness (cIMT), in the hemodialysis (HD) patients. In this cross-sectional study, serums were obtained from 50 stable chronic HD patients and 39 healthy controls. The serum levels of sTWEAK, Vitamin D, intact parathyroid hormone (iPTH) in both groups, and cIMT were determined in HD patients by standard methods. Serum levels of sTWEAK were higher [808.8 (521.6–5032.4) pg/ml vs. 664.4 (487.4–2955.8) pg/ml (p = 0.006)] and Vitamin D levels were lower [13.4 (2.5–153) ng/ml vs. 27.8 (18.4–59.0) ng/ml (p = 0.001)] in the hemodialysis patients than in the healthy control. No important correlation was found between sTWEAK Vitamin D levels (r = 0.010/p = 0.946), and mean right(r = ?0.194/p = 0.178) and left (r = 0.061/p = 0.673) cIMT in the HD patients. Our study shows that sTWEAK levels are elevated in HD patients. This elevation has no association with the cIMT.     

Troponin T and Heart Type Fatty Acid Binding Protein (h-Fabp) as Biomarkers in Patients Presenting with Chest Pain

Acute coronary syndrome (ACS) is a term for a range of clinical signs and symptoms suggestive of myocardial ischemia. It results in functional and structural changes and ultimately releasing protein from injured cardiomyocytes. These cardiac markers play a major role in diagnosis and prognosis of ACS. This study aims to assess the efficacy of heart type fatty acid binding protein (h-FABP) as a marker for ACS along with the routinely used hs-TropT. In our observational study, plasma h-FABP (cut-off 6.32 ng/ml) and routinely done hs-Trop T (cutoff 0.1 and 0.014 ng/ml) were estimated by immunometric laboratory assays in 88 patients with acute chest pain. Based on the clinical and laboratory test findings the patients were grouped into ACS (n = 41) and non-ACS (n = 47). The diagnostic sensitivity, specificity, NPV, PPV and ROC curve at 95 % CI were determined. Sensitivity of hs-TropT (0.1 ng/ml), hs-TropT (0.014 ng/ml) and h-FABP were 53, 86 and 78 % respectively and specificity for the same were 98, 73 and 70 % respectively. Sensitivity, specificity and NPV calculated for a cut-off combination of hs-TropT 0.014 ng/ml and h-FABP was 100, 51 and 100 % respectively. These results were substantiated by ROC analysis. Measurement of plasma h-FABP and hs-TropT together on admission appears to be more precise predictor of ACS rather than either hs-Trop T or h-FABP.