Syed Kashif Nawaz

Genetic etiology of coronary artery disease considering NOS 3 gene variant rs1799983

Reduced production of nitric oxide due to rs1799983 single nucleotide polymorphism in nitric oxide synthase 3 gene (NOS3) may enhance the risk of coronary artery disease. The association of rs1799983 polymorphism with coronary artery disease was investigated in the local population of Pakistan. Study consisted of 376 individuals, out of which 198 were coronary artery disease patients and 178 were normal healthy individuals. Allele-specific polymerase chain reaction (PCR) based strategy was used for the detection of different genotypes of rs1799983 polymorphism. PCR amplification results were obtained for 354 samples. Frequency of T allele was higher as compared to G allele in our population. Strong association between rs1799983 and coronary artery disease was observed (p < 0.01). TT genotype was found to enhance 5.717 times the risk of coronary artery disease (odds ratio (OR): 5.717; 95% confidence interval (95% CI) 3.586–9.115). On the basis of present results, it can be concluded that rs1799983 is strongly associated with coronary artery disease in our population and TT genotype of this polymorphism enhanced the risk of coronary artery disease in Pakistani population.

Association of the rs10757274 SNP with coronary artery disease in a small group of a Pakistani population.

Objective: The present study aimed to investigate the association between the rs10757274 SNP (present on locus 9p21 in the gene for CDKN2B-AS1) and coronary artery disease (CAD) in a local population of Pakistan. Methods: It was a case-control study. An allele-specific PCR-based strategy was used for the identification of genotypes. A total of 350 samples were used for the investigation, out of which 220 samples were CAD patients and 130 samples were normal healthy individuals. Effects of parameters, like family history of CAD, smoking, presence of diabetes, and hypertension, in changing the chances of CAD were studied. Odds ratio was estimated with 95% confidence interval. Results: A strong association was observed between CAD and factors, like smoking (OR: 1.666; 95% CI: 1.042-2.664), presence of hypertension (OR: 26.55; 95% CI: 15.95-44.20), diabetes (OR: 3.009; 95% CI: 1.841-4.920), and family history of CAD (OR: 4.9; 95% CI: 2.965-8.099). Results for the association between the genotype on the basis of rs10757274 showed a strong association between the GG genotype and the occurrence of CAD (OR: 9.603; 95% CI: 5.746-16.05). Conclusion: The present results suggest the importance of the 9p21 locus in modulating the chances of CAD.

Prevalence of cardiovascular diseases in Punjab, Pakistan: a cross-sectional study

AimThe purpose of the present study was to measure the frequency of CVDs and some of the risk factors and to familiarize people with information on the high rates of mortality and morbidity due to CVDs in the studied areas of Punjab, Pakistan.SubjectsCardiovascular diseases (CVDs) are the leading cause of sudden death. CVDs are a major health problem in Pakistan, and the number of patients is increasing daily.AimThe purpose of the present study was to measure the frequency of CVDs and some of the risk factors and to familiarize people with information on the high rates of mortality and morbidity due to CVDs in the studied areas of Punjab, Pakistan.MethodA cross-sectional study was conducted to investigate the prevalence of cardiovascular diseases in the local population of 53 cities in Punjab, Pakistan. A total of 6351 individuals were contacted to collect data using a questionnaire from October 2014 to September 2015. Data were collected directly by meeting the participants or indirectly through relatives and friends.ResultsOf the participants, 49.2% (3127/6351) were male and 50.8% (3224/6351) female. The data showed that 17.5% (1109/6351) of the population had CVDs with 16.6% (519/3127) being male and 18.3% (590/3224) female.ConclusionThis study concluded that CVDs are a serious problem for both genders and affected 17.5% of the studied population. Diseases are more common in females than males with young age of onset. An inactive lifestyle, low level of activity and family history of disease could be disease risk factors in the study area.

Role of MyD88-adaptor-like gene polymorphism rs8177374 in modulation of malaria severity in the Pakistani population

INTRODUCTION The present study was designed to investigate the association between rs8177374 polymorphism and malaria symptoms due to exposure of Plasmodium vivax and Plasmodium falciparum. MATERIALS AND METHODS A total of 454 samples were included in the study (228 malaria patients and 226 healthy individuals). Malaria patients, divided into P. vivax and P. falciparum groups on the basis of the causative species of Plasmodium, were categorized into mild and severe on the basis of clinical outcomes according to WHO criteria. Healthy individuals were used as controls. Allele specific PCR based strategy was used for the identification of rs8177374 SNP. RESULTS MyD88-adaptor-like gene polymorphism was associated with susceptibility to malaria (p<0.001). C allele frequency (0.74) was higher in the population compared to T allele frequency (0.26). CT genotype increased the susceptibility of malaria (OR: 2.661; 95% CI: 1.722-4.113) and was positively associated with mild malaria (OR: 5.609; 95% CI: 3.479-9.044, p=0.00). On the other hand, CC genotype was associated with severe malaria (OR: 3.116; 95% CI: 1.560-6.224, p=0.00). P. vivax infection rate was higher in CT genotype carriers compared to other genotypes (OR: 3.616; 95% CI: 2.219-5.894, p<0.001). CONCLUSION MyD88-adaptor-like/TIR domain containing adaptor protein polymorphism for single nucleotide polymorphism rs8177374 is related with the susceptibility of malaria.

Association between Genetic Polymorphism and Risk of von Willebrand Disease in Pakistan

von Willebrand disease (VWD) is an inherited, genetically and clinically heterogeneous hemorrhagic disorder. The most common cause of this disease is mutation in the gene that encodes protein von Willebrand factor (VWF) which is responsible for blood clotting. The current study was designed to investigate the role of genetic polymorphisms with the onset of VWD in population of Pakistan. Three exonic variants (c.3445T>C; c.4975C>T; c.7603C>T) from VWF gene were used for the genotyping purpose. The current study employed a case-control association design involving 43 VWD patients and 100 healthy controls from Pakistani population. The genetic reason of VWD was investigated using the allele specific PCR. The significant (P < 0.05) allelic association was found between all three exonic variants and VWD. The CT genotype of these variants was noticed to be associated with significantly higher risk of VWD [odds ratio (95% CI): 14.7 (4.546–47.98), 26.71 (7.281–97.98), and 21.5 (5.806–80.01) for c.3445T>C, c.4975C>T, and c.7603C>T, resp.] while genotypes CC (c.4975C>T) and TT (c.3445T>C and c.7603C>T) were having protective effect against the disease. However, replicated studies are needed for elaborating the role of these SNPs.

Association of rs1800668 polymorphism in glutathione peroxidase- 1 gene and risk of rheumatoid arthritis in Pakistani population.

Objective: To investigate the role of glutathione peroxidase 1 (GPX1) C/T polymorphism (rs1800668) in modulating the chances of Rheumatoid arthritis (RA) in Pakistani population. Methods: A total of 400 individuals including 200 controls and 200 patients of RA, were genotyped. Detection of rs1800668 polymorphism was carried out using PCR based amplification strategy (allele specific). Results: The results for Hardy Weinberg Equilibrium (HWE) indicated that the allele frequencies for GPX1 polymorphism were not deviant from HWE in whole population under observation. The statistical analysis indicated that significant association existed between rs1800668 polymorphism and RA (p<0.01). CT genotype increased the risk of RA development by 1.8582 times (OR: 1.8582; 95% CI 1.2154 to 2.8409). CC genotype was found to have protective effect against the disease development (OR: 0.5133; 95% CI 0.3403 to 0.7742) while TT genotype was found to have association with RA development but the risk level was marginal (OR: 1.5319; 95% CI 0.6124 to 3.8322). Conclusion: The present finding suggests the importance of GPX1 C/T polymorphism (rs1800668) in development of RA in Pakistani population. The protective role of CC genotype against the development of RA in local population was also observed.

Role of S180L polymorphism in etiology of malaria caused by Plasmodium falciparum in a small group of Pakistani population

The aim of our study was to investigate the role of S180L polymorphism in modulation of acquisition of malaria caused by Plasmodium falciparum in a small group of Pakistani population. A total of 133 individuals including 60 controls and 73 patients of malaria, caused by Plasmodium falciparum, were genotyped using allele-specific PCR. Ninety-two samples successfully demonstrated the PCR amplification results, while forty-one samples could not be genotyped due to failure in PCR amplification. The allele frequency for S180L polymorphism was deviant from Hardy-Weinberg equilibrium (HWE) of the population under observation. Association was found between the observed polymorphism and the occurrence of malaria caused by Plasmodium falciparum (p = 0.01). Chances of malaria caused by Plasmodium falciparum were low in CC genotype carriers in comparison to other genotypes (Odds ratio: 0.3016; 95% CI: 0.124-0.729). The present findings suggest that S180L polymorphism is important in modulating the probability of acquisition of malaria caused by Plasmodium falciparum in Pakistani population. The CC genotype plays a protective role in local population against this type of malaria.