Are our people health conscious? results of a patients survey in Karachi, Pakistan

BACKGROUND: Life style is known to influence health and may be responsible for certain diseases. There is a need to document the life style on health among the Pakistani population. METHODS: The study was conducted on patients visiting the Family Practice Center, the Aga Khan University, Karachi. A questionnaire was used to collect information on the demographic profile, and the life style on health. The ethical requirements for conducting the study were met. RESULTS: 393 patients were surveyed. The majority were young married men, in either private or government service. Preference for consumption of fats/oils, sweets, spicy foods, salt, fruits/vegetables, tea, coffee, cola drinks and alcohol was found among 103 (26%), 84 (22%), 86 (22%), 110 (28%), 239 (61%), 319 (81%), 117 (30%), 253 (64%) and 13 (03%) respondents respectively. Hand washing after defecation, before eating food and after work was seen among 341 (87%), 296 (75%) and 256 (65%) respondents respectively. Brushing of teeth after eating food, before breakfast and bedtime was seen in 56 (14%), 346 (88%) and 176 (45%) respondents respectively. Preventive dental check-up was practiced by 102 (26%) of the respondents. Sleep of less than 6 hours per day among 74 (19%), water consumption of less than 1 liter daily among 84 (21%) and fish consumption on once a week basis among 173 (44%) respondents was found. Tobacco and betel nuts use was found among 69 (17%) and 79 (20%) respondents. CONCLUSIONS: We have documented a clear need to raise public awareness on the issue of life style on health. There is a need and we strongly recommend debate and further research, along with interventional strategies in line with the available evidence on healthy life style

Association study of two interleukin-1 gene loci with essential hypertension in a Pakistani Pathan population

An association study of IL-1 beta -511C/T and IL-1 RN 86 bp VNTR polymorphisms with essential hypertension was carried out in a sample population of 500 Pakistani Pathan subjects selected randomly, comprising groups of 235 subjects with hypertension and 265 controls. The distribution of both genotypes and alleles was not statistically different in cases and controls. In conclusion, IL-1 beta -511C/T and IL-1 RN 86 bp VNTR do not contribute to the aetiology of essential hypertension in the Pakistani Pathan population investigated here

Genetic risk factors for ischaemic stroke and its subtypes (the METASTROKE Collaboration): a meta-analysis of genome-wide association studies

<p>Background - Various genome-wide association studies (GWAS) have been done in ischaemic stroke, identifying a few loci associated with the disease, but sample sizes have been 3500 cases or less. We established the METASTROKE collaboration with the aim of validating associations from previous GWAS and identifying novel genetic associations through meta-analysis of GWAS datasets for ischaemic stroke and its subtypes.</p> <p>Methods - We meta-analysed data from 15 ischaemic stroke cohorts with a total of 12 389 individuals with ischaemic stroke and 62 004 controls, all of European ancestry. For the associations reaching genome-wide significance in METASTROKE, we did a further analysis, conditioning on the lead single nucleotide polymorphism in every associated region. Replication of novel suggestive signals was done in 13 347 cases and 29 083 controls.</p> <p>Findings - We verified previous associations for cardioembolic stroke near PITX2 (p=2·8×10−16) and ZFHX3 (p=2·28×10−8), and for large-vessel stroke at a 9p21 locus (p=3·32×10−5) and HDAC9 (p=2·03×10−12). Additionally, we verified that all associations were subtype specific. Conditional analysis in the three regions for which the associations reached genome-wide significance (PITX2, ZFHX3, and HDAC9) indicated that all the signal in each region could be attributed to one risk haplotype. We also identified 12 potentially novel loci at p<5×10−6. However, we were unable to replicate any of these novel associations in the replication cohort.</p> <p>Interpretation - Our results show that, although genetic variants can be detected in patients with ischaemic stroke when compared with controls, all associations we were able to confirm are specific to a stroke subtype. This finding has two implications. First, to maximise success of genetic studies in ischaemic stroke, detailed stroke subtyping is required. Second, different genetic pathophysiological mechanisms seem to be associated with different stroke subtypes.</p&gt

Dairy food products: good or bad for cardiometabolic disease?

Prevalence of type 2 diabetes mellitus (T2DM) is rapidly increasingly and is a key risk for CVD development, now recognised as the leading cause of death globally. Dietary strategies to reduce CVD development include reduction of saturated fat intake. Milk and dairy products are the largest contributors to dietary saturated fats in the UK and reduced consumption is often recommended as a strategy for risk reduction. However, overall evidence from prospective cohort studies does not confirm a detrimental association between dairy product consumption and CVD risk. The present review critically evaluates the current evidence on the association between milk and dairy products and risk of CVD, T2DM and the metabolic syndrome (collectively, cardiometabolic disease). The effects of total and individual dairy foods on cardiometabolic risk factors and new information on the effects of the food matrix on reducing fat digestion are also reviewed. It is concluded that a policy to lower SFA intake by reducing dairy food consumption to reduce cardiometabolic disease risk is likely to have limited or possibly negative effects. There remain many uncertainties, including differential effects of different dairy products and those of differing fat content. Focused and suitably designed and powered studies are needed to provide clearer evidence not only of the mechanisms involved, but how they may be beneficially influenced during milk production and processing

Physical activity, smoking, and genetic predisposition to obesity in people from Pakistan:the PROMIS study

Background: Multiple genetic variants have been reliably associated with obesity-related traits in Europeans, but little is known about their associations and interactions with lifestyle factors in South Asians. Methods: In 16,157 Pakistani adults (8232 controls; 7925 diagnosed with myocardial infarction [MI]) enrolled in the PROMIS Study, we tested whether: a) BMI-associated loci, individually or in aggregate (as a genetic risk score - GRS), are associated with BMI; b) physical activity and smoking modify the association of these loci with BMI. Analyses were adjusted for age, age(2), sex, MI (yes/no), and population substructure. Results: Of 95 SNPs studied here, 73 showed directionally consistent effects on BMI as reported in Europeans. Each additional BMI-raising allele of the GRS was associated with 0.04 (SE = 0.01) kg/m(2) higher BMI (P = 4.5 x 10(-14)). We observed nominal evidence of interactions of CLIP1 rs11583200 (P-interaction = 0.014), CADM2 rs13078960 (P-interaction = 0.037) and GALNT10 rs7715256 (P-interaction = 0.048) with physical activity, and PTBP2 rs11165643 (P-interaction = 0.045), HIP1 rs1167827 (P-interaction = 0.015), C6orf106 rs205262 (P-interaction = 0.032) and GRID1 rs7899106 (P-interaction = 0.043) with smoking on BMI. Conclusions: Most BMI-associated loci have directionally consistent effects on BMI in Pakistanis and Europeans. There were suggestive interactions of established BMI-related SNPs with smoking or physical activity

Genomics of lipid metabolism: Identifying novel causal pathways and new therapeutic targets for reducing risk of coronary heart disease

Coronary heart disease (CHD) is one of the leading causes of death worldwide; mortality rates are expected to continue to rise over the coming decades. Circulating lipids have been shown to be strongly and linearly associated with risk of CHD; however, despite considerable efforts to demonstrate causality, available evidence is conflicting and insufficient. Study of the underlying metabolic pathways implicated in the association between lipids and CHD would help to disentangle and elucidate these complex relationships. Direct infusion high-resolution mass spectrometry was performed on 5,551 participants from the Pakistan Risk of Myocardial Infarction Study; raw data were then processed, cleaned, and normalized to extract signals corresponding to 444 known lipid metabolites. Cross-correlations of lipid metabolites and their correlations with circulating lipids were examined, and the association of principal components of lipid metabolites with CHD risk factors was assessed. Genome-wide analyses were conducted to analyze the association of each lipid metabolite with 7.2 million genotyped and imputed single nucleotide polymorphisms (SNPs). Following conditional analyses on the lead SNP within each loci, we identified genome-wide significant associations at 148 independent metabolic loci and 54 novel loci. We then used functional annotation to link the variants associated with each metabolite to the most probable causal genes, and two-sample Mendelian randomization to examine the causal effect of lipid metabolites on risk of CHD. Analyses of circulating lipid metabolites in large epidemiological studies could lead to enhanced understanding of mechanisms for CHD development and identification of novel causal pathways and new therapeutic targets

Latent activity of curcumin against leishmaniasis in vitro

In this study the anti-proliferative effect of curcumin (curcuma longa) that is the active ingredient of ground dried rhizome has been studied against three local and three reference leishmanial strains, Leishmania major, Leishmania tropica and Leishmania infantum (Pakistani isolate). Curcumin has shown an average IC50 of 5.3mM against promastigotes of various leishmanial strains which is much lower as compared with pentamidine that is one of the basic treatments against leishmaniasis. The main draw back attributed to these assays performed on promastigotes is the heterogeneity of results compared with those obtained with intracellular amastigotes or with in vivo effect. We also tested activity of curcumin against axenic amastigote like cells (AALC) of L. major strain (MHOM/PK/88/DESTO). Curcumin proves to be far more potent then pentamidine against AALC which further strengthens the fact about its leishmaniacidal activity

Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10(-8), in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms

A comprehensive 1000 Genomes-based genome-wide association meta-analysis of coronary artery disease

Existing knowledge of genetic variants affecting risk of coronary artery disease (CAD) is largely based on genome-wide association studies (GWAS) analysis of common SNPs. Leveraging phased haplotypes from the 1000 Genomes Project, we report a GWAS meta-analysis of 185 thousand CAD cases and controls, interrogating 6.7 million common (MAF>0.05) as well as 2.7 million low frequency (0.005<MAF<0.05) variants. In addition to confirmation of most known CAD loci, we identified 10 novel loci, eight additive and two recessive, that contain candidate genes that newly implicate biological processes in vessel walls. We observed intra-locus allelic heterogeneity but little evidence of low frequency variants with larger effects and no evidence of synthetic association. Our analysis provides a comprehensive survey of the fine genetic architecture of CAD showing that genetic susceptibility to this common disease is largely determined by common SNPs of small effect siz