Influence of cytokine gene polymorphisms on proinflammatory/anti-inflammatory cytokine imbalance in premature coronary artery disease.

BACKGROUND: Genetic information has the potential to create a more personalised, prompt, early and accurate risk evaluation. The effect of these genetic variants on the serum biomarker levels (phenotype) needs to be studied to assess their potential causal role in the pathogenesis of premature coronary artery disease (PCAD). Objectives were to determine the genotypic distribution of interleukin (IL) 18, tumour necrosis factor-α (TNFA), IL6 and IL10 single nucleotide polymorphisms (SNPs) in Pakistani PCAD cases and disease free controls and to study the effect of these gene polymorphisms on the serum cytokine levels (IL18, TNFA, IL6 and IL10) and cytokine imbalance (IL18:IL10 and TNFA:IL10). MATERIAL AND METHODS: The case-control study was carried out in National University of Sciences and Technology, Islamabad in collaboration with the Cardiovascular Genetics Institute, University College London, UK. Subjects (n=340) with >70% stenosis in at least a single major coronary artery on angiography were taken as PCAD cases along with 310 angiographically verified controls. ELISA was performed for measuring the concentrations of serum IL18, TNFA, IL6 and IL10. Genotyping was done using TAQMAN assay. RESULTS: The risk allele frequencies (RAFs) of rs1800795 (IL6) and rs187238 (IL18) cytokine gene promoter SNPs were significantly higher in the PCAD cases as compared with the controls. Serum IL18 and IL10 levels were significantly greater in the IL18 rs187238 GG genotype patients while serum IL18 and IL6 levels were significantly higher in patients having the IL6 rs1800795 CC genotype. IL18 SNP rs1946519 significantly altered the IL18, TNFA, IL6, IL18/IL10 and TNFA/IL10 ratio levels followed by TNFA SNP rs1800629 which significantly altered the serum levels of IL18, IL18:IL-0 and TNFA:IL10 ratios. CONCLUSIONS: The association of the selected SNPs with differential serum cytokine levels especially the cytokine imbalance points towards their potential causal role in the immune inflammatory pathogenic pathway of PCAD.

Injudicious use of laboratory facilities in tertiary care hospitals at Rawalpindi, Pakistan: a cross-sectional descriptive study.

BACKGROUND: In recent years inappropriate and excessive use of clinical laboratory facilities has become a cause of concern and has led to concurrent rise in the laboratory errors and the health care costs. The aim of the study was to find out the frequency of incomplete laboratory request forms, inappropriate test requests at various professional levels and the financial impact of uncollected reports at Armed Forces Institute of Pathology (AFIP) and Combined Military Hospital (CMH) Laboratory Rawalpindi. METHODS: The cross-sectional descriptive study was conducted during a three month period from April to June 2012 at AFIP and CMH Laboratory Rawalpindi. A total of 1000 laboratory request forms were collected and scrutinized for completion from AFIP (n=500) and CMH Rawalpindi laboratory (n=500). 536 request forms of costly/specialized tests from different departments of AFIP were studied to find out the professional level of test request. The total number of tests performed at AFIP during the study period and number of uncollected reports were noted. The financial impact of these uncollected reports was also calculated. Collection of data and sorting were done manually. Patient confidentiality was maintained. Microsoft excel software and SPSS-17 were used for analysis. The study was approved by the Institutional Ethical Review Committee. RESULTS: Out of a total of 1000 forms studied none was completely filled with clinical notes being present in only 2.4% and 13% of forms sent to CMH and AFIP respectively. 62% of the expensive investigations were requested by specialists while 38% were ordered by residents and general practitioners but the percentage of avoidable expensive tests ordered by the general practitioners and residents was significantly higher than the specialists(p<0.001). A total of 9026 (40%) and 5046 (22%) diagnostic test reports were not collected from the Chemical pathology and Hematology departments respectively. Financial impact of uncollected reports from all the departments at AFIP collectively amounted to Pakistani Rupees (PKR) 3338201. CONCLUSION: Processing incomplete laboratory request forms and injudicious use of laboratory facilities leads to incorrect interpretation of laboratory test results affecting outcome of the overall treatment.

Pro/anti-inflammatory cytokines in the pathogenesis of premature coronary artery disease.

Proinflammatory interleukin-18 (IL-18), high-sensitivity C-reactive protein (hS-CRP), tumor necrosis factor-alpha (TNF-alpha), and anti-inflammatory IL-10 are involved in the pathogenesis of atherosclerosis. The aim of this study was to determine the imbalance between pro- and anti-inflammatory cytokines in premature coronary artery disease (PCAD) and their association with the degree of angiographic atherosclerotic blockade. A case-control study was carried out at the National Institute of Heart Diseases, Rawalpindi, Pakistan. Three hundred eighty-five stable coronary artery disease patients aged <45 years were screened. A total of 172 subjects participated in this study, comprising 98 PCAD patients and 74 angionegative controls. Serum IL-10, IL-18, and TNF-alpha were measured using enzyme-linked immunosorbent assay and hS-CRP was analyzed using Immulite 1000. The mean age of the patients was 40 ± 4.23 years (69 men and 9 women). Serum IL-18, TNF-alpha, hS-CRP, and IL-18/IL-10 ratio were significantly raised in PCAD patients (P<0.01), whereas IL-10 was moderately increased (P<0.05) when compared with controls. Serum IL-18 and hS-CRP were significantly raised in patients with 86%-100% stenosis (n=57) when compared with patients with 71%-85% stenosis (n=41) (P<0.05). Serum IL-18, TNF-alpha, IL-18/IL-10 ratio, and hS-CRP significantly correlated (P<0.01) with the degree of angiographic blockade. Pro/anti-inflammatory cytokines play a vital role in the pathogenesis of PCAD and have potential to identify the degree of atherosclerosis.

Synergistic effects of iron deficiency and lead exposure on blood lead levels in children.

BACKGROUND: Lead poisoning is a well recognized environmental health problem in children. Independent association of iron deficiency and lead exposure with elevated blood lead level (BLL) has been reported. Whether iron deficiency in combination with chronic lead exposure increases BLL and susceptibility to its harmful effects in children needs to be elucidated. METHODS: In this case-control study, 246 children were randomly recruited. They comprised 123 children of lead smelters/battery recycle plant workers living close to the industries at Wah/Gujranwala, Pakistan (lead exposed group) and 123 children living 30 km away from the industrial area (controls). Blood lead analysis was carried out on the anodic stripping voltammeter lead analyzer 3010B. Blood counting was done on a Sysmex hematological analyzer and serum ferritin was determined by kit method on Immulite-1000. RESULTS: Of the 123 children in each group, 42 (34%) were iron deficient in the exposed group while 35 (28%) in the controls. The children's median age was 4 years (69 males and 54 females in each group). Lead exposed iron deficient children had significantly higher BLL median (quartile) 13.1 µg/dL (10.1-16.8) as compared with 9.6 µg/dL (7.6-10.3) in the iron deficient controls (P<0.05). Elevated BLL level was found in 31% of the lead exposed children and in 11% of the controls. Lead exposed children revealed a stronger negative correlation (r= -0.54; P=0.001) between BLL and serum ferritin than the controls (r=-0.36; P=0.01). CONCLUSION: Iron deficiency in combination with lead exposure synergistically elevates blood lead levels and susceptibility to its harmful effects in children.

Lead exposure and its adverse health effects among occupational worker's children.

Lead exposure is an important environmental health problem particularly affecting the children of occupational workers living in the lead-contaminated environment. The objectives of the study were to find out the frequency, potential sources and adverse health effects of elevated blood lead level (BLL) in the children of lead-related occupational workers. It was a comparative cross-sectional study. A total of two hundred forty six children aged 1-6 years, comprising an equal number (n = 123) from lead smelters/battery recycle plant workers living close to the industries at Wah/Gujranwala, Pakistan (lead-exposed group) and those living 30 km away from the industrial area (controls) were included. Demographic and clinical data of each subject was collected. Blood lead analysis was carried out by using kits on the lead analyzer (3010 B ESA, USA). Biochemical tests of renal and hepatic profile were analyzed on Selectra E auto analyzer. The median age of children was 4 years; comprising of 69 boys and 54 girls. The lead-exposed children had significantly high BLLs median (range) 8.1 (1-20.9) microg/dL as compared to controls 6.7 (1-13.3) microg/dL (p 10 microg/dL) in 38 (31%) as compared with 14 (11%) in controls. Hematopoietic, renal, and hepatic functions were significantly impaired in the lead-exposed children. In conclusion, the children of lead-related occupational workers have significantly increased frequency (31%) of lead poisoning. The potential source of lead overexposure in these children may be indirect through father's clothes and contaminated environment at home. Increased lead accumulation adversely affects health of these children.