Lian L.-H.,University of Malaya |
Loke A.-C.,Pharmacogenomics Laboratory |
Zainal N.Z.,University of Malaya
Asian Biomedicine | Year: 2013
Background: Alterations of the serotonergic neurotransmission system have been suspected to be involved in the pathogenesis of neuropsychiatric disorders including major depressive disorders (MDD). Tryptophan hydroxylase (TPH) 1 gene has been proposed as a candidate gene for MDD in Caucasian and Chinese populations from different countries. However, there is no comprehensive study of TPH1 gene in the MDD samples from Malaysia. Objective:We examined the possible association between the two intronic polymorphisms, A218C (rs1800532) and A779C (rs1799913), and MDD in the three main ethnic groups of the Malaysian population. Methods:We enrolled and genotyped 265 unrelated patients and 332 unrelated healthy subjects using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results: We observed no significant association in the genotype and allele frequencies between the MDD patients and control subjects for either of the tested polymorphisms, whereas the linkage disequilibrium (LD) among the three ethnicities and combined samples were strong (D' >0.8). Conclusion: In summary, our preliminary study suggests that the TPH1 gene may be associated with the MDD in the Indian population. However, further studies using larger sample sizes are necessary in order to verify this result. The ability of obtaining the MDD patient's genotypic data, in addition to the diagnosis of the myriad of symptoms, will most definitely be able to assist clinicians to better care, manage, and treat their patients.
Ramu P.,Pharmacogenomics Laboratory |
Umamaheswaran G.,Pharmacogenomics Laboratory |
Shewade D.G.,Pharmacogenomics Laboratory |
Swaminathan R.P.,JIPMER |
And 3 more authors.
International Journal of Human Genetics | Year: 2011
Genetic variants of renin angiotensin system (RAS) gene play a significant role in the pathogenesis of essential hypertension and cardiovascular diseases. In the present study, we investigated the association of RAS gene polymorphisms with hypertension by analyzing the polymorphisms ACE ID, AGT T207M, M268T and AGT1R A1166C in 462 hypertensive patients and 444 healthy subjects. Genotyping was determined by allele specific PCR, PCR-RFLP and RT-PCR Taqman assay. The ACE ID heterozygous (OR=1.5: 95% CI: 1.0-2.3, p<0.05) and ACE DD homozygous genotype (OR=1.7: 95% CI: 1.2-2.8, p<0.01) was found to be significantly associated with hypertension. There was no significant association between AGT T207M, M268T and AGT1R A1166C gene polymorphisms and hypertension. Gender-specific analysis showed ACE ID heterozygous genotypes were positively associated with hypertension among male hypertensives (OR=1.9: 95% CI: 1.1-2.6, p<0.01). Significant gene-gene interaction was observed between ACE ID and AGT M268T polymorphisms (OR=2.0; 95% CI: 1.2-3.5, p<0.01). Our results suggest that ACE ID polymorphism is associated with hypertension. Further, gene-gene interaction between ACE ID and AGT M268T gene polymorphisms further modified the risk of essential hypertension. © Kamla-Raj 2011.
Zain S.M.,Pharmacogenomics Laboratory |
Zain S.M.,University of Malaya |
Mohamed Z.,Pharmacogenomics Laboratory |
Mohamed Z.,University of Malaya |
And 6 more authors.
Pharmacogenetics and Genomics | Year: 2015
Background Orexigenic actions mediated by neuropeptide-Y (NPY) promote body weight regulation. Genetic variations in the NPY gene could therefore influence susceptibility to obesity, but results have been conflicting. We have carried out, for the first time, a case-control study to examine the effect of NPY rs16147 and rs5574 variants with the risk of obesity in Asians and also a meta-Analysis to summarize the effect of these variants including that of the widely studied rs16139. Materials and methods Genotypes and biochemistry data were determined for 942 children (262 cases and 680 controls) recruited from 23 randomly selected schools in Malaysia. Relevant articles were identified from Pubmed, Embase, Web of Science and Google Scholar. Data were extracted and summary estimates of the association between the NPY variants and obesity were examined. Results The frequency of the rs16147 T allele was significantly higher in the cases than controls (odds ratio 1.27, 95% confidence interval 1.04-1.55, P=0.022), whereas the rs5574 T allele was significantly higher in the controls (odds ratio 0.76, 95% confidence interval 0.61-0.96, P=0.020). In addition, NPY rs16147 was significantly correlated with obesity parameters including BMI, waist circumference, triglyceride and body fat percentage (P<0.05). Meta-Analysis including nine case-control studies further confirmed the findings of the association of the two variants with the risk of obesity and also found that rs16139 was associated with increased risk. Conclusion This study suggests that NPY rs16147 T and rs16139 C minor alleles are associated with increased risk, whereas the minor allele T of the rs5574 is associated with a reduced risk of obesity. © Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Kumar S.,Pharmacogenomics Laboratory |
Kumar A.S.A.,Pharmacogenomics Laboratory |
Padmapriya R.,Pharmacogenomics Laboratory |
Chandrasekaran A.,Pharmacogenomics Laboratory
Indian Journal of Pharmacology | Year: 2013
Background: The model of pulse plethysmograph using inhalational salbutamol 400 mcg is studied well to assess endothelium dependent vasodilation. Endothelial nitric oxide synthase (eNOS) gene polymorphism may influence the response to salbutamol in healthy subjects. Aim: To find the effect of polymorphisms 894G>T and-786T>C of eNOS gene on endothelium dependent vasodilation in healthy subjects. Materials and Methods: One hundred and two south Indian healthy subjects of either sex, aged between 18 to 35 years were recruited for the study. The digital volume pulse (DVP)was measured by pulse plethysmograph before and after salbutamol 400mcg inhalation. Three predose and five postdose recordings of DVP were measured. The average change in the DVP parameters namely reflection index (RI) and stiffness index (SI) were determined. The eNOS894G>T and-786T>C gene polymorphism were genotyped using polymerase chain reaction followed by restriction fragment length polymorphism. The percentage changes in RI and SI from predose baseline recordings were calculated and compared between the genotype groups. Results: The genotype and allele frequency of study subjects were in Hardy-Weinberg equilibrium. The changes in DVP parameters were not significantly different between the genotype groups. Conclusion: eNOS polymorphism do not affect salbutamol evoked endothelium dependent vasodilation in the model of pulse plethysmograph in healthy subjects.