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Biomedical subjects

Hafiz M R Khan

Publications and source records attributed to Hafiz M R Khan.

6 recordsLinked to original sources

Metabolic syndrome in aboriginal Canadians: prevalence and genetic associations.

OBJECTIVES: The prevalence rates of type 2 diabetes (T2DM) and coronary heart disease (CHD) in Ontario Oji-Cree are among the world's highest. Since metabolic syndrome (MetS) increases risk of T2DM and CHD, we characterized prevalence and putative genetic determinants of MetS in Oji-Cree. METHODS AND RESULTS: In 515 adult (> or = 18 years old) and 115 adolescent (< 18 years old) Oji-Cree subjects, using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria, we determined that 29.9% of Oji-Cree adults, and 43.4% of adults > or = 35 years of age, had MetS. Furthermore, 33.9 and 8.7% of female Oji-Cree adults and adolescents, respectively, had MetS. Increased waist girth and depressed HDL cholesterol were the most prevalent individual MetS components, while increased blood pressure was least prevalent. AGT T174M, GNB3 825C>T, and APOC3 -455T>C genotypes were significantly associated with MetS (P = 0.018, 0.0056, and 0.029, respectively) for female adults, whereas FABP2 A54T genotype was associated with MetS (P = 0.040) for female adolescents. CONCLUSIONS: The high MetS prevalence in Oji-Cree adults, especially women, is consistent with their high risk of T2DM and CHD. Functional polymorphisms in three candidate genes for plasma lipoproteins and blood pressure were associated with MetS in adult Oji-Cree. Furthermore, several female adolescents met the adult MetS criteria, suggesting that the genesis of MetS begins in youth, especially among aboriginal females.

Adolescent↗

Differences between carotid wall morphological phenotypes measured by ultrasound in one, two and three dimensions.

Ultrasound measurements are both surrogate markers and risk factors for atherosclerosis end points. Carotid intima-media thickness (IMT) is most commonly used, but ultrasound can also define structures in higher spatial dimensions, such as total plaque area (TPA) and total plaque volume (TPV). Because there are minimal data regarding the relationship between IMT, TPA and TPV, we measured these variables in 272 Oji-Cree subjects. We found pairwise correlations for IMT:TPA, IMT:TPV and TPA:TPV of 0.507, 0.588 and 0.846, respectively (transformed variables, all P <0.0001). In a subset of 168 subjects with complete cardiovascular risk factor data, we performed multivariate regression analysis to identify sources of variation for IMT, TPA and TPV. We found that the ultrasound traits showed different correlations with individual cardiovascular risk factors. In particular, IMT was significantly associated with hypertension, TPA with smoking and plasma cholesterol, and TPV with diabetes. Therefore, these ultrasound measures of carotid artery morphology, while somewhat correlated, likely represent distinctive quantitative traits with different biological determinants, as underscored by different risk factor associations in the multivariate regression analysis. Because the measurements have different implications and determinants, investigators might need to be selective about the particular measurements they choose for specific applications.

Adult↗

Genetic variation in PPARG encoding peroxisome proliferator-activated receptor gamma associated with carotid atherosclerosis.

BACKGROUND AND PURPOSE: Peroxisome proliferator-activated receptor gamma is a crucial molecule in atherogenesis because it is associated with metabolic risk factors such as obesity and diabetes and also plays a key role in subcellular metabolism of arterial wall macrophage foam cells. Genetic variation in PPARG has been associated with metabolic and cardiovascular end points. METHODS: We investigated the relationship between 2 common PPARG polymorphisms, namely P12A and c.1431C>T, and carotid atherosclerosis in a sample of 161 Canadian aboriginal people. Dependent variables were carotid intima media thickness (IMT), assessed using B-mode ultrasonography, and total carotid plaque volume (TPV), assessed using 3D ultrasound. RESULTS: Using multivariate analysis, we found that subjects with > or =1 PPARG A12 allele had less carotid IMT than others (0.72+/-0.03 versus 0.80+/-0.02 mm; P=0.0045), with no between-genotype difference in TPV. In contrast, subjects with the PPARG c.1431T allele had greater TPV than others (124+/-18.4 versus 65.1+/-23.7 mm3; P=0.0079), with no between-genotype difference in IMT. CONCLUSIONS: The findings show an association between PPARG genotypes and carotid arterial phenotypes, and further reflect the prevailing view that the PPARG A12 allele protects against deleterious phenotypes. Also, whereas IMT and TPV are somewhat correlated with each other, they might also represent distinct traits with discrete determinants representing different stages of atherogenesis.

Adult↗

Optimizing RNA extraction yield from whole blood for microarray gene expression analysis.

OBJECTIVES: Microarray analysis of gene expression profiles of blood leukocytes has many potential clinical and research applications. DESIGN AND METHODS: We used the PAXgene Blood RNA System to prepare RNA from the whole blood of normal volunteers using two incubation times followed by gene expression profiling using the Affymetrix HU133A GeneChip. CONCLUSIONS: Longer incubation gave a significantly higher RNA yield and samples that were satisfactory for microarray analysis, with excellent pairwise correlations between replicates.

Gene Expression Profiling↗

Venn analysis as part of a bioinformatic approach to prioritize expressed sequence tags from cardiac libraries.

OBJECTIVES: We needed to sort expressed sequence tags (ESTs) from human cardiac expression libraries. DESIGN AND METHODS: We annotated DNA sequence text files of 35,152 cardiac ESTs using our search and annotation tool called Multiblast.pl. We generated lists of the most prevalent ESTs in each library, and using a novel Venn tool, we grouped ESTs that were common to all or exclusive to particular libraries. RESULTS: Hypothetical protein KIAA0553 was expressed 120 times among 917 ESTs from an adult cardiac library (13.1%) compared only once among 8075 ESTs from fetal cardiac libraries (P < 10(-114)), this was confirmed using Northern analysis. We collated biochemical features of KIAA0553 and determined DNA polymorphism frequencies. We also used the Venn tool to specify genes that were uniquely expressed in hypertrophic cardiomyocytes. CONCLUSIONS: Annotating ESTs and sorting them using Venn analysis can help specify new candidate disease genes from the current lists of "hypothetical proteins".

Amino Acid Sequence↗