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Maria Khan,
Asif Rasheed,
Saman Hashmi,
Moazzam Zaidi,
Muhammad Murtaza,
Saba Akhtar,
Lajpat Bansari,
Nabi Shah,
Maria Samuel,
Sadaf Raza, [......],
Tasnim Ahsan,
S M Munir,
Shoukat Ali,
Khalid Mehmood,
Karim Ullah Makki,
Muhammad Masroor Ahmed,
Niaz Sheikh,
Abdul Rauf Memon, Philippe M Frossard,
Ayeesha Kamran Kamal
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ABSTRACT: BACKGROUND: There are no descriptions of stroke mechanisms from intracranial atherosclerotic disease in native South Asian Pakistanis. METHODS: Men and women aged ≥18 years with acute stroke presenting to four tertiary care hospitals in Karachi, Pakistan were screened using magnetic resonance angiography/transcranial Doppler scans. Trial of ORG 10172 in Acute Stroke Treatment criteria were applied to identify strokes from intracranial atherosclerotic disease. RESULTS: We studied 245 patients with acute stroke due to intracranial atherosclerotic disease. Two hundred thirty scans were reviewed. Also, 206/230 (89·0%) showed acute ischaemia. The most frequent presentation was with cortically based strokes in 42·2% (87/206) followed by border-zone infarcts (52/206, 25·2%). Increasing degrees of stenosis correlated with the development of both cortical and border-zone strokes (P = 0·002). Important associated findings were frequent atrophy (166/230, 72·2%), silent brain infarcts (66/230, 28%) and a marked lack of severe leukoaraiosis identified in only 68/230 (29·6%). A total of 1870 arteries were studied individually. Middle cerebral artery was the symptomatic stroke vessel in half, presenting with complete occlusion in 66%. Evidence of biological disease, symptomatic or asymptomatic was identified in 753 (40·2%) vessels of which 543 (72%) were significantly (>50%) stenosed at presentation. CONCLUSION: Intracranial atherosclerotic disease is a diffuse process in Pakistani south Asians, with involvement of multiple vessels in addition to the symptomatic vessel. The middle cerebral artery is the most frequent symptomatic vessel presenting with cortical embolic infarcts. There is a relative lack of leukoaraiosis. Concomitant atrophy, silent brain infarcts and recent ischaemia in the symptomatic territory are all frequently associated findings.
International Journal of Stroke 09/2012; · 2.38 Impact Factor
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John F Peden,
Jemma C Hopewell,
Danish Saleheen,
John C Chambers,
Jorg Hager,
Nicole Soranzo,
Rory Collins,
John Danesh,
Paul Elliott,
Martin Farrall, [......],
Francesca Gori,
Roberto Marchioli,
Suthesh Sivapalaratnam,
John J P Kastelein,
Mieke D Trip,
Eirini V Theodoraki,
George V Dedoussis,
Jamie C Engert,
Salim Yusuf,
Sonia S Anand
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ABSTRACT: Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD), a modest number considering the apparent heritability of CAD. All of these variants have been discovered in European populations. We report a meta-analysis of four large genome-wide association studies of CAD, with ∼575,000 genotyped SNPs in a discovery dataset comprising 15,420 individuals with CAD (cases) (8,424 Europeans and 6,996 South Asians) and 15,062 controls. There was little evidence for ancestry-specific associations, supporting the use of combined analyses. Replication in an independent sample of 21,408 cases and 19,185 controls identified five loci newly associated with CAD (P < 5 × 10(-8) in the combined discovery and replication analysis): LIPA on 10q23, PDGFD on 11q22, ADAMTS7-MORF4L1 on 15q25, a gene rich locus on 7q22 and KIAA1462 on 10p11. The CAD-associated SNP in the PDGFD locus showed tissue-specific cis expression quantitative trait locus effects. These findings implicate new pathways for CAD susceptibility.
Nature Genetics 03/2011; · 35.53 Impact Factor
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Danish Saleheen,
Saman K Hashmi,
Moazzam Zaidi,
Asif Rasheed,
Muhammed Murtaza,
Adil Abbas,
Sana Nasim,
Mustafa Qadir Hameed,
Fahad Shuja,
Muhammad Jawad Sethi,
Imad Hussain,
Kamran Shahid,
Hamza Khalid,
Usman Ahmad, Philippe M Frossard,
Muhammad Ishaq
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ABSTRACT: Cardiovascular diseases (CVD) are increasing at an alarming rate in South Asia. High blood pressure is a modifiable risk factor for CVD. In this study, we evaluated the control of blood pressure and the prevalence of cardiovascular risk factors in patients with hypertension.
A cross-sectional study was conducted in 50 primary health care centres throughout Pakistan. Individuals with a documented history of hypertension, receiving pharmacological therapy, were enrolled and evaluated for the control of their blood pressure.
The recommended therapeutic control of hypertension (systolic blood pressure <140 mmHg, diastolic blood pressure <90 mmHg) was seen in only 6.4% of the study participants. Values of both the mean systolic and diastolic blood pressures in all subjects were higher than the desired therapeutic levels (P<0.001). There was a high prevalence in the study population of established but modifiable risk factors of CVD, such as smoking (30.5%), hypercholesterolemia (59.5%) and sedentary lifestyle (43.5%). Lack of therapeutic control of systolic blood pressure was found significantly associated with age, hypercholesterolemia and sedentary lifestyle (P<0.05).
Patients being treated at primary health care centres in Pakistan have inadequate control of high blood pressure. Evidence-based continuous education of primary health care physicians is a necessary intervention for optimizing treatment strategies and achieving better therapeutic control of hypertension in our population.
Journal of Evaluation in Clinical Practice 12/2010; 16(6):1081-4. · 1.23 Impact Factor
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Hypertension Research 06/2009; 32(5):423. · 2.58 Impact Factor
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Ayeesha Kamran Kamal,
Fawad Taj,
Babar Junaidi,
Asif Rasheed,
Moazzam Zaidi,
Muhammed Murtaza,
Naved Iqbal,
Fahad Hashmat,
Syed Vaqas Alam,
Uzma Saleem, [......],
Khalid Mahmood,
Niaz Sheikh,
Karim Ullah Makki,
Muhammad Masroor Ahmed,
Abdul Rauf Memon,
Mohammad Wasay,
Nadir Ali Syed,
Bhojo Khealani, Philippe M Frossard,
Danish Saleheen
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ABSTRACT: Intracranial stenosis is the most common cause of stroke among Asians. It has a poor prognosis with a high rate of recurrence. No effective medical or surgical treatment modality has been developed for the treatment of stroke due to intracranial stenosis. We aim to identify risk factors and biomarkers for intracranial stenosis and to develop techniques such as use of transcranial doppler to help diagnose intracranial stenosis in a cost-effective manner.
The Karachi Intracranial Stenosis Study (KISS) is a prospective, observational, case-control study to describe the clinical features and determine the risk factors of patients with stroke due to intracranial stenosis and compare them to those with stroke due to other etiologies as well as to unaffected individuals. We plan to recruit 200 patients with stroke due to intracranial stenosis and two control groups each of 150 matched individuals. The first set of controls will include patients with ischemic stroke that is due to other atherosclerotic mechanisms specifically lacunar and cardioembolic strokes. The second group will consist of stroke free individuals. Standardized interviews will be conducted to determine demographic, medical, social, and behavioral variables along with baseline medications. Mandatory procedures for inclusion in the study are clinical confirmation of stroke by a healthcare professional within 72 hours of onset, 12 lead electrocardiogram, and neuroimaging. In addition, lipid profile, serum glucose, creatinine and HbA1C will be measured in all participants. Ancillary tests will include carotid ultrasound, transcranial doppler and magnetic resonance or computed tomography angiogram to rule out concurrent carotid disease. Echocardiogram and other additional investigations will be performed at these centers at the discretion of the regional physicians.
The results of this study will help inform locally relevant clinical guidelines and effective public health and individual interventions.
BMC Neurology 02/2009; 9:31. · 2.17 Impact Factor
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ABSTRACT: Angiotensin-converting enzyme (ACE) plays an important role in the development of systemic lupus erythematosus (SLE) because its end-product, angiotensin II, plays an integral role in the regulatory system responsible for endothelial control and vascular tone, systems that are commonly affected in patients with SLE. Additionally, ACE inhibitors have been shown to retard the progression of SLE and lupus nephritis. Our goal was to investigate whether ACE gene polymorphisms are associated with increasing severity of SLE. We genotyped 39 SLE patients of varying disease severity from a homogenous Asian population and 79 control subjects for ACE I/D and 2350 G > A dimorphisms. All patients met the American College of Rheumatology (ACR) criteria for SLE and their disease severity was measured using Systemic Lupus Activity Measure (SLAM). The "A" allele was found to be associated with increase in severity of SLE with the AA genotype present only in severe disease. No association with SLE in general, compared to healthy subjects, was found with either dimorphism. We also examined the transmission of haplotypes as defined by these polymorphisms. The D and A alleles were found in strong linkage disequilibrium especially in severe SLE. The DA-haplotype was more frequent in severe SLE, than mild to moderate disease. Our findings suggest that DNA sequence variation in the ACE gene influences disease progression and severity of SLE.
Saudi journal of kidney diseases and transplantation: an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia 09/2008; 19(5):761-6.
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ABSTRACT: Obesity and hypertension are two major inter-related cardiovascular risk factors. Decrease in adiposity is one of the most effective preventive measures not only in decreasing the overall cardiovascular risk but also the blood pressure. This cross-sectional study measured the effect of various measures of adiposity on blood pressure in normal healthy subjects of Pakistani origin. 400 normotensive subjects (247 males and 153 females) were included in this study. Along with data on co-morbid conditions, two blood pressure readings and several anthropometric measurements were recorded. Age and gender specific analysis was done. Following the WHO cutoffs for Asians, about 52% of our sample population was found to be overweight or obese. Age was not associated with blood pressure indices in males; however it was strongly associated with all blood pressure indices in females. Greater Body Mass Index (BMI), Waist Circumference (WC) and Waist to Height Ratio (WHTR) were associated with higher Systolic and Diastolic Blood pressure. Increasing age was also associated with higher levels of BMI, WC and WHTR. Anthropometric variables however, were more strongly associated with blood pressure indices than age in this sample population. In conclusion, we found WC and WHTR to be strongly associated with blood pressure indices in normotensive Pakistani males.
International journal of cardiology 03/2008; 124(2):259-62. · 7.08 Impact Factor
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Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 02/2008; 18(1):64-5. · 0.34 Impact Factor
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ABSTRACT: Pantothenate kinase-associated neurodegeneration is an autosomal-recessive disorder associated with the accumulation of iron in the basal ganglia. The disease presents with dystonia, rigidity, and gait impairment, leading to restriction of activities and loss of ambulation. The disorder is caused by defective iron metabolism associated with mutations in the PANK2 gene, which codes for the pantothenate kinase enzyme. We report on a mutation screen conducted in two siblings to establish a molecular diagnosis of the disease and a genetic test for the family.
Pediatric Neurology 11/2007; 37(4):296-8. · 1.52 Impact Factor
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ABSTRACT: Takayasu disease is a giant cell arteritis, primarily affecting the aorta and its main branches, particularly over the first 1.5 cm. It is more common in South-East Asian countries and in young females, whose clinical manifestations range from asymptomatic to catastrophic neurological impairment.
We report on a Pakistani family in which five of seven siblings, aged 12 to 19 years, are affected with atypical Takayasu arteritis. The proband is a 14-year-old male who presented with sudden, painless loss of vision. He was found to have absent pulses, retinal changes and magnetic resonance angiography (MRA) findings diagnostic of Takayasu arteritis. In addition, though, he had decreased intraocular pressure, murmur of mitral valve prolapse, as well as atypical involvement of the aorta as visualized in MRA and decreased renal blood flow; these last three findings are not usual features of the disease. The unique involvement in the aorta indicates that this patient corresponds to yet another sub-type in the angiographic classification of TA. Four siblings of the proband are asymptomatic but fulfill the diagnostic criteria of the American College of Rheumatology. This is the first reported multiplex family with Takayasu arteritis, in which more than two members meet the diagnostic criteria.
Previous reports indicate possible HLA associations of Takayasu disease in Japanese patients. Our present study indicates both that there may be clinical and etiological heterogeneity in Takayasu disease, and the possibility that an autosomal recessive form of the disease exists.
Medical science monitor: international medical journal of experimental and clinical research 09/2007; 13(8):CS101-5. · 1.70 Impact Factor
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ABSTRACT: This retrospective, case-control study was carried out to find putative correlations of eNOS G894T polymorphism with essential hypertension (EHT) amongst adult Pakistani Pathans. We investigated a sample population of 332 (154 men, 178 women) comprising groups of 146 hypertensives (HTs) and 186 normotensives (NTs) by assays based on polymerase chain reaction followed by restriction endonuclease analysis. The distribution of the genotypes or alleles was not statistically different in hypertensive and normotensive groups. In conclusion, the present study in a population of Pakistani adult Pathans does not support the association of the eNOS gene G894T polymorphism to essential hypertension.
International journal of cardiology 04/2007; 116(1):113-5. · 7.08 Impact Factor
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Danish Saleheen,
Shaheen Khanum,
Shajjia R Haider,
Aisha Nazir,
Usman Ahmad,
Hamza Khalid,
Imad Hussain,
Fahad Shuja,
Kamran Shahid,
Aisha Habib, Philippe M Frossard
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ABSTRACT: ATP-binding cassette transporter 1 (ABCA1) is a trans-membrane protein responsible for the efflux of cholesterol and phospholipids across the cell membrane, an essential step in the reverse cholesterol transport system. This study investigates the effect of five non-synonymous SNPs of ABCA1 gene on plasma HDL-C levels in Pakistani individuals free of ischemic heart disease and stroke.
Five non-synonymous SNPs were selected after sequencing ABCA1 gene in patients of Hypoalphalipoproteinemia. The presence of these SNPs was then checked in 200 individuals by using PCR-RFLP. Plasma glucose and lipid fractions were measured in fasting state. Ethical approval was obtained from the Ethical Review Committee, Aga Khan University and informed consent was obtained from all subjects.
LL genotype of V825L polymorphism was associated with decreased levels of HDL-C [-0.17 (-0.32 to -0.19); P=0.02] and P774 allele showed a significant increase in HDL-C levels as compared to T774 allele [-0.15 (-0.18 to -0.02); P=0.01]. R219K, A399V and V771M polymorphisms did not show any association with levels of HDL-C, LDL-C, cholesterol and triglycerides. Haplotype analysis between R219K and V825L polymorphisms showed a unique interaction between R219 allele and L825 allele. The RL haplotype was found to be associated with decreased levels of HDL-C [-0.12 (-0.22 to -0.03); P=0.001].
ABCA1 polymorphisms are associated with varying levels of HDL-C in Pakistani individuals. These results warrant further investigations as ABCA1 polymorphisms may have a major role in the high incidence of cardiovascular disorders in South Asians.
International journal of cardiology 02/2007; 115(1):7-13. · 7.08 Impact Factor
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ABSTRACT: Poor adherence is one of the biggest obstacles in therapeutic control of high blood pressure. The objectives of this study were (i) to measure adherence to antihypertensive therapy in a representative sample of the hypertensive Pakistani population and (ii) to investigate the factors associated with adherence in the studied population.
A cross-sectional study was conducted on a simple random sample of 460 patients at the Aga Khan University Hospital (AKUH) and National Institute of Cardiovascular Diseases, Karachi, from September 2005-May 2006. Adherence was assessed using the Morisky Medication Adherence Scale (MMAS), with scores ranging from 0 (non-adherent) to 4 (adherent). In addition to MMAS, patient self-reports about the number of pills taken over a prescribed period were used to estimate adherence as a percentage. AKU Anxiety and Depression Scale (AKU-ADS) was incorporated to find any association between depression and adherence. At a cut-off value of 80%, 77% of the cases were adherent. Upon univariate analyses, increasing age, better awareness and increasing number of pills prescribed significantly improved adherence, while depression showed no association. Significant associations, upon multivariate analyses, included number of drugs that a patient was taking (P<0.02) and whether he/she was taking medication regularly or only for symptomatic relief (P<0.00001).
Similar to what has been reported worldwide, younger age, poor awareness, and symptomatic treatment adversely affected adherence to antihypertensive medication in our population. In contrast, monotherapy reduced adherence, whereas psychosocial factors such as depression showed no association. These findings may be used to identify the subset of population at risk of low adherence who should be targeted for interventions to achieve better blood pressure control and hence prevent complications.
PLoS ONE 01/2007; 2(3):e280. · 4.09 Impact Factor
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International Journal of Cardiology 07/2006; 110(2):259-60. · 7.08 Impact Factor
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ABSTRACT: Cystic fibrosis is a multi-system genetic disorder caused by mutation in the cystic fibrosis conductance transmembrane regulator (CFTR) gene located on chromosome 7. In United Arab Emirates (UAE), pattern of CF causing gene mutations is different than rest of the Arabs in the region and 95% of CF in Emirati families has been found due to two mutations only - -p.S549R(T>G) and p.F508del. We report the case of a homozygote for a mutation 3120 +1G-->A in the Emirati population detected in a young boy referred to CF and Respiratory Clinic at Tawam Hospital (Al Ain, UAE) for screening CFTR gene.
Journal of the College of Physicians and Surgeons--Pakistan: JCPSP 03/2006; 16(2):139-40. · 0.34 Impact Factor
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ABSTRACT: South Asian population has a high incidence of coronary artery disease. There are a number of risk factors that are almost unique to the south Asians. The classical risk factors do not account for such high rates of CHD as are present in south Asia. We have discussed some important aspects of CHD that can help in improving prevention in south Asia.
International Journal of Cardiology 03/2006; 107(2):289-90. · 7.08 Impact Factor
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ABSTRACT: The angiotensin converting enzyme gene (ACE) is a candidate gene for an individual's genetic susceptibility to left ventricular hypertrophy (LVH). LVH has long been thought to be an end point of essential hypertension (EH), rather than a separate entity, though it is influenced by a unique set of hormonal, vascular and genetic factors. In this study, we attempted to determine whether two representative polymorphisms of the ACE gene, ACE I/D and 2350 G>A, known to be associated with EH and to influence plasma ACE levels most significantly, could implicate ACE as a quantitative trait locus (QTL) for LVH. We carried out a retrospective, case-control study of the two ACE polymorphisms amongst 180 nationals (50 LVH patients and 130 controls) from the United Arab Emirates--an ethnic group characterized by no alcohol intake and no cigarette smoking--for correlations with LVH. Clinical diagnosis of LVH was based on echocardiographic and ECG criteria. ACE I/D and 2350 G>A genotypes were determined by PCR and restriction digestion. Univariate and multivariate logistic regression analyses revealed an association between ACE polymorphisms and LVH. Haplotype analysis further supported this finding. ACE I/D and ACE 2350 G>A polymorphisms are in strong linkage disequilibrium and are associated with LVH, suggesting that ACE is likely to be a QTL for LVH.
Neuro endocrinology letters 09/2005; 26(4):393-6. · 1.30 Impact Factor
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ABSTRACT: To date, the human G-protein beta 3 subunit (GNB3) gene and some of its variants represent some of the best examples of genetic influences that are involved in the determination of hypertension and obesity, which make it a sensible candidate gene for type 2 diabetes. To assess the influence of GNB3 in type II diabetes mellitus (NIDDM), we carried out a retrospective, case-control study of variant GNB3 825C>T for putative correlations with NIDDM amongst nationals from the United Arab Emirates (Emirati) - an ethnic group characterized by no alcohol intake and no cigarette smoking. We investigated a sample population of 510 Emirati (257 men, 253 women) comprising two groups - 254 controls and 256 patients with clinical diagnoses of type 2 diabetes (cases). The GNB3 C825T dimorphism showed an association with NIDDM Chi2 =22.5, 2 df, P<0.001). Further analysis revealed that the GNB3 T/T 825 genotype was positively associated with NIDDM (Yates corrected Chi2=20.6, 2 df, P<0.001; odds ratio of 2.44 with a 95% confidence interval of 1.64 - 3.63) compared to pooled CC/CT genotypes. Our data shows that GNB3 T825 allele may be involved in the pathogenesis of DM through a pathway that is different from the one implicated in obesity.
Neuro endocrinology letters 05/2005; 26(2):87-8. · 1.30 Impact Factor
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ABSTRACT: The objectives of this project were two-fold: to identify the genetic mutation that has been detected as an MboI dimorphism in intron 9 of the human renin (REN) gene and to confirm a previously reported, putative association between the REN MboI dimorphism and clinical diagnosis of essential hypertension (EHT) in a population of Gulf Arabs from the United Arab Emirates. Sequencing of the MboI dimorphic site was carried out on DNA of randomly chosen cases and controls. A retrospective case-control study was carried out in 689 unrelated subjects (326 first-time, clinically diagnosed hypertensives and 363 age- and gender-matched normotensive subjects), selected from the resident population of the Abu Dhabi Emirate. A polymerase chain reaction/MboI-RFLP based method was employed to compare genotype and allele distributions. Nucleotide sequences at the MboI site of the cut and uncut alleles were determined to be GATC and GGTC, respectively. This A>G mutation is located 10,631 base pairs (bp) 3' to the start of the REN gene, and 79 bp 3' to the end of exon 9. The genotype distributions of the REN 10631A>G dimorphism were found to be significantly different between hypertensive and normotensive subjects (x2= 42.29, df=2, p<0.001). Frequencies of A alleles were 0.54 in EHT vs. 0.37 in normotensive subjects, which is even more demarcated than what was found previously. The frequency of AA genotypes was higher in the hypertensive group than in the normotensive group (34.7% vs. 14.0%). The quantification of the association of A alleles with increased risk of EHT was assessed with corresponding odds ratios (OR), which gave the following values: OR of GG vs. AG genotypes, 1.3 (95% confidence interval [CI]: 0.90-1.88); OR of GG vs. AA, 3.75 (95% CI: 2.41-5.86). In conclusion, REN 10631A alleles are significantly associated with EHT in the Emirati population. This has now been found in two different and therefore independent sample populations from the Abu Dhabi Emirate. Moreover, this genetic effect seems to be acting in a recessive fashion. Hence, either the REN gene itself, or another gene that is in linkage disequilibrium with REN 10631A>G, is implicated in the pathogenesis of EHT in Emirati.
Hypertension Research 05/2005; 28(4):339-44. · 2.58 Impact Factor
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ABSTRACT: Among the many candidates that could be implicated in underlying an individual's genetic susceptibility to human essential hypertension (EHT), the renin gene (REN) is particularly appealing because of its central role in the renin-angiotensin-aldosterone system and of its demonstrated functional role in hypertensive animal models.We had previously shown that two dimorphic sites of the human REN gene (BglI in intron 1 and MboI in intron 9) were individually associated with hypertension in two independent populations.We used here a retrospective, case-control design to investigate the haplotype distributions of alleles combining BglI and MboI sites in two groups of subjects (144 hypertensives and 96 normotensives) from the United Arab Emirates (UAE), a genetically homogeneous ethnic population with no history of smoking or alcohol consumption. There was a marked difference in the distribution of haplotypes among normotensive vs. hypertensive subjects (χ2 = 29.87, 3 df, p=10−6). The odds ratio of the association of [BglI(+)-MboI(+)] haplotypes with increased risk for hypertension was 4.43 (95% CI: 2.41–8.19, Yates-corrected p = 3 × 10−7).Genetic variations of the REN (or of a nearby) gene that may be in linkage disequilibrium with REN [BglI(+)-MboI(+)] alleles could play a role in contributing to increased individual's genetic susceptibility to EHT among UAE nationals studied here.
Biogenic Amines 04/2005; 19(2):79-88.
