Biomedical subjects

Amjad P Khan

Publications and source records attributed to Amjad P Khan.

5 recordsLinked to original sources

PubMed2006

Predominance of interaction among wild-type alleles of CYP11B2 in Himalayan natives associates with high-altitude adaptation.

Sojourners visiting high-altitude (HA) (>2500 m) are susceptible to HA disorders; on the contrary, HA natives are well adapted to the extreme hypoxic environment. High aldosterone levels are believed to be involved in HA disorders, we, therefore, envisaged role of CYP11B2 gene variants in HA adaptation and therefore investigated the -344T/C, intron-2 conversion (Iw/Ic), K173R, and A5160C polymorphisms. In addition, polymorphisms in AGT, AT1R, ATP1A1, ADRB2, and GSTP1 genes were also investigated. The study comprised of 662 subjects, comprising of 426 Himalayan highlanders (HLs) and 236 lowlanders (LLs). The -344T/C and K173R polymorphisms were found to be in complete linkage disequilibrium. The wild-type allele -344T and combination of wild-type homozygous genotypes between -344T/C, Iw/Ic, and A5160C polymorphisms, containing all the six wild-type alleles were over-represented in the HLs (p < 0.0001, and p = 0.008, respectively). The wild-type haplotypes -344T-Iw, -344T-5160A, and -344T-Iw-5160A also showed over-representation in the HLs (p < 0.0001). Furthermore, greater the number of wild-type alleles, lower was the ARR (p < 0.05). The genotype distribution in remaining genes did not differ. To conclude, the over-representation of wild-type -344T allele, genotype combinations and haplotypes of CYP11B2, and their correlation with lower aldosterone levels associate with HA adaptation in the HLs. Such an allelic presentation in sojourners may help them cope with adverse HA environment.

Adaptation, Physiological↗

PubMed2004

Renin angiotensin aldosterone system and ACE I/D gene polymorphism in high-altitude pulmonary edema.

INTRODUCTION: People who visit high altitude are exposed to a stressful environment, and many of them suffer from altitude-induced conditions, including high altitude pulmonary edema (HAPE). We investigated the renin angiotensin aldosterone system (RAAS) and the possible association of angiotensin converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism in the development of HAPE in Indian men. METHODS: Subjects were all low-altitude natives: 19 men who developed HAPE within 1-3 d of arrival at 3000 to 3800 m (patients); and 20 age-matched men who did not develop HAPE during a period of a month or more at > or = 3500 m (controls). We recorded the arterial oxygen saturation (Sao2), heart rate (HR), and blood pressure (BP) of both groups and measured their levels of plasma renin activity (PRA), ACE, aldosterone, and serum electrolytes. Polymerase chain reaction was used to investigate a 287 base pair alu repeat sequence I/D polymorphism in the ACE gene. RESULTS: Compared with controls, patients showed a significantly lower Sao2 and a higher HR. They also had significantly higher plasma PRA, aldosterone, ACE, and serum sodium (Na+) and potassium (K+). No significant difference was observed in ACE I/D allele frequencies. DISCUSSION: The results suggested that RAAS is involved in the development of HAPE in low-altitude natives, but there is no association of ACE I/D gene polymorphism with HAPE.

Adult↗

PubMed2003

Association of high-altitude systemic hypertension with the deletion allele-of the angiotensin-converting enzyme (ACE) gene.

People who visit high-altitude areas are exposed to a stressful environment and a good percentage of them suffer from high-altitude-induced diseases, including systemic hypertension. Identification of genetic markers for high-altitude-induced diseases would help to reduce the rate of morbidity/mortality from such diseases. The development of systemic hypertension on exposure to high altitude (3,500 m) for 30 days in otherwise normotensive natives of low-altitudes was investigated. The angiotensin-converting enzyme (ACE) insertion/deletion (I/D) genotypes and renin-angiotensin-aldosterone system were simultaneously studied. In the hypertensives during their stay at high altitude, the ACE D allele frequency was significantly higher than in the normotensives (0.67 versus 0.32 chi(2)(1) = 10.6, P < 0.05). In the normotensives during their stay at high altitude, there was no significant increase in plasma aldosterone levels despite increased plasma renin activity. Results of the present study suggest that environmental changes and pre-existing genetic factors, namely the ACE D allele, might be two of the factors predisposing natives of low altitudes to systemic hypertension, a polygenic disease, at high altitude.

Adaptation, Physiological↗

PubMed2002

Variations in angiotensin-converting enzyme gene insertion/deletion polymorphism in Indian populations of different ethnic origins.

The pattern of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism in the Indian population is poorly known. In order to determine the status of the polymorphism, young unrelated male army recruits were screened. The population had cultural and linguistic differences and lived in an environment that varied significantly from one region to another. Analysis of the genotype, showed higher frequency of the insertion allele in four of the five groups i.e. I allele frequency was significantly higher (P < 0.05) in Dogras, Assamese and Kumaonese. The deletion allele frequency was comparatively higher in the fifth group that belonged to Punjab. A correlation was observed between the genotype and enzyme activity. Involvement of a single D allele in the genotype enhanced the activity up to 37.56 3.13%. The results suggested ethnic heterogeneity with a significant gene cline with higher insertion allele frequency. Such population-based data on various polymorphisms can ultimately be exploited in pharmacogenomics.

Ethnicity↗

PubMedDate not supplied

Imaging of proteolytic activity using a conditional cell surface receptor.

Programmed cell death (apoptosis) is a ubiquitous means utilized by multicellular organisms for elimination of unwanted cells during development and homeostasis. Dysregulated apoptosis is implicated in an array of clinical disorders including cancer, autoimmune diseases, neurodegenerative disorders, and ischemia. During programmed cell death, a series of proteases, known as caspases, with different specificities play crucial roles in the apoptotic process. Caspase-3, a group II cysteine aspartate protease, recognizes and cleaves substrates harboring the amino acid sequence aspartic acid-glutamic acid-valine-aspartic acid (DEVD), and it plays an important role in the terminal phase of apoptosis. Here we report the development of a novel imaging platform for sensing the activation of cellular proteases. A recombinant chimeric protein was constructed, composed of a cell-surface-targeted single-chain antibody (sFv) fused to a Golgi retention signal. The DEVD tetrapeptide sequence was included between the single-chain antibody and the Golgi retention signal as a caspase-3 protease cleavage site. When expressed in cultured cells this fusion protein was localized to Golgi bodies and was not detected on the cell surface. Induction of apoptosis resulted in cleavage of the fusion protein releasing the single-chain antibody from the Golgi retention signal in a caspase-dependent manner. As a result, in cells undergoing apoptosis the single-chain antibody was visualized at the cell surface by immunofluorescence microscopy. The expression of sFv on the surface of cells in a protease-dependent manner provides a unique opportunity for real-time imaging through the use of targeted nanoparticles. This methodology may provide for a multimodal noninvasive real-time imaging of apoptosis and a new opportunity for high-throughput screening of cell-death-modulating therapeutic agents.

Animals↗