Commenced in January 2007
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Edition: International
Paper Count: 6

Search results for: SNPs

6 Genotypic and Allelic Distribution of Polymorphic Variants of Gene SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) and Their Association to the Clinical Response to Metformin in Adult Pakistani T2DM Patients

Authors: Sadaf Moeez, Madiha Khalid, Zoya Khalid, Sania Shaheen, Sumbul Khalid

Abstract:

Background: Inter-individual variation in response to metformin, which has been considered as a first line therapy for T2DM treatment is considerable. In the current study, it was aimed to investigate the impact of two genetic variants Leu125Phe (rs77474263) and Gly64Asp (rs77630697) in gene SLC47A1 on the clinical efficacy of metformin in T2DM Pakistani patients. Methods: The study included 800 T2DM patients (400 metformin responders and 400 metformin non-responders) along with 400 ethnically matched healthy individuals. The genotypes were determined by allele-specific polymerase chain reaction. In-silico analysis was done to confirm the effect of the two SNPs on the structure of genes. Association was statistically determined using SPSS software. Results: Minor allele frequency for rs77474263 and rs77630697 was 0.13 and 0.12. For SLC47A1 rs77474263 the homozygotes of one mutant allele ‘T’ (CT) of rs77474263 variant were fewer in metformin responders than metformin non-responders (29.2% vs. 35.5 %). Likewise, the efficacy was further reduced (7.2% vs. 4.0 %) in homozygotes of two copies of ‘T’ allele (TT). Remarkably, T2DM cases with two copies of allele ‘C’ (CC) had 2.11 times more probability to respond towards metformin monotherapy. For SLC47A1 rs77630697 the homozygotes of one mutant allele ‘A’ (GA) of rs77630697 variant were fewer in metformin responders than metformin non-responders (33.5% vs. 43.0 %). Likewise, the efficacy was further reduced (8.5% vs. 4.5%) in homozygotes of two copies of ‘A’ allele (AA). Remarkably, T2DM cases with two copies of allele ‘G’ (GG) had 2.41 times more probability to respond towards metformin monotherapy. In-silico analysis revealed that these two variants affect the structure and stability of their corresponding proteins. Conclusion: The present data suggest that SLC47A1 Leu125Phe (rs77474263) and Gly64Asp (rs77630697) polymorphisms were associated with the therapeutic response of metformin in T2DM patients of Pakistan.

Keywords: Diabetes, T2DM, SLC47A1, Pakistan, polymorphism.

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5 In vivo Therapeutic Potential of Biologically Synthesized Silver Nanoparticles

Authors: Kalakotla Shanker, G. Krishna Mohan

Abstract:

Nowadays, nanoparticles are being used in pharmacological studies for their exclusive properties such as small size, more surface area, biocompatibility and enhanced solubility. In view of this, the present study aimed to evaluate the antihyperglycemic potential of biologically synthesized silver nanoparticles (BSSNPs) and Gymnema sylvestre (GS) extract. The SEM and SEM analysis divulges that the BSSNPs were spherical in shape. EDAX spectrum exhibits peaks for the presence of silver, carbon, and oxygen atoms in the range of 1.0-3.1 keV. FT-IR reveals the binding properties of active bio-constituents responsible for capping and stabilizing BSSNPs. The results showed increased blood glucose, huge loss in body weight and downturn in plasma insulin. The GS extract (200 mg/kg, 400 mg/kg), BSSNPs (100 mg/kg, 200 mg/kg) and metformin 50 mg/kg were administered to the diabetic rats. BSSNPs at a dose level of 200 mg/kg (b.wt.p.o.) showed significant inhibition of (p<0.001) blood glucose levels as compared with GS extract treated group. The results obtained from study indicate that the BSSNP shows potent anti-diabetic activity.

Keywords: BSSNP, G.sylvetre, wistar rats, antihyperglycemic activity.

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4 Association between Single Nucleotide Polymorphism of Calpain1 Gene and Meat Tenderness Traits in Different Genotypes of Chicken: Malaysian Native and Commercial Broiler Line

Authors: Abtehal Y. Anaas, Mohd. Nazmi Bin Abd. Manap

Abstract:

Meat Tenderness is one of the most important factors affecting consumers' assessment of meat quality. Variation in meat tenderness is genetically controlled and varies among breeds, and it is also influenced by environmental factors that can affect its creation during rigor mortis and postmortem. The final postmortem meat tenderization relies on the extent of proteolysis of myofibrillar proteins caused by the endogenous activity of the proteolytic calpain system. This calpain system includes different calcium-dependent cysteine proteases, and an inhibitor, calpastatin. It is widely accepted that in farm animals including chickens, the μ-calpain gene (CAPN1) is a physiological candidate gene for meat tenderness. This study aimed to identify the association of single nucleotide polymorphism (SNP) markers in the CAPN1 gene with the tenderness of chicken breast meat from two Malaysian native and commercial broiler breed crosses. Ten, five months old native chickens and ten, 42 days commercial broilers were collected from the local market and breast muscles were removed two hours after slaughter, packed separately in plastic bags and kept at -20ºC for 24 h. The tenderness phenotype for all chickens’ breast meats was determined by Warner-Bratzler Shear Force (WBSF). Thawing and cooking losses were also measured in the same breast samples before using in WBSF determination. Polymerase chain reaction (PCR) was used to identify the previously reported C7198A and G9950A SNPs in the CAPN1 gene and assess their associations with meat tenderness in the two breeds. The broiler breast meat showed lower shear force values and lower thawing loss rates than the native chickens (p<0.05), whereas there were similar in the rates of cooking loss. The study confirms some previous results that the markers CAPN1 C7198A and G9950A were not significantly associated with the variation in meat tenderness in chickens. Therefore, further study is needed to confirm the functional molecular mechanism of these SNPs and evaluate their associations in different chicken populations.

Keywords: CAPNl, chicken, meat tenderness, meat quality, SNPs.

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3 The Role of MAOA Gene in the Etiology of Autism Spectrum Disorder in Males

Authors: Jana Kiskov√°, Dana Gabrikov√°

Abstract:

Monoamine oxidase A gene (MAOA) is suggested to be a candidate gene implicated in many neuropsychiatric disorders, including autism spectrum disorder (ASD). This meta-analytic review evaluates the relationship between ASD and MAOA markers such as 30 bp variable number tandem repeats in the promoter region (uVNTR) and single nucleotide polymorphisms (SNPs) by using findings from recently published studies. It seems that in Caucasian males, the risk of developing ASD increase with the presence of 4- repeat allele in the promoter region of MAOA gene whereas no differences were found between autistic patients and controls in Egyptian, West Bengal and Korean population. Some studies point to the importance of specific haplotype groups of SNPs and interaction of MAOA with others genes (e. g. FOXP2 or SRY). The results of existing studies are insufficient and further research is needed.

Keywords: Autism spectrum disorder, MAOA, uVNTR, single nucleotide polymorphism.

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2 Genetic Polymorphisms and Haplotype Structure of the Organic Cation Transporter 1 Gene in the Zulu Population of South Africa

Authors: N. Hoosain, S. Nene, B. Pearce, C. Jacobs, M. Du Plessis, M. Benjeddou

Abstract:

Organic cation transporter (OCT) 1could influence an individual’s response to various treatments and increase their susceptibility to diseases.Genotypic and allelic frequencies of nineteen non-synonymous and one intronic Single Nucleotide Polymorphism (SNP) from the OCT1 gene were determined in 101 unrelated healthy Zulu participants, using a SNaPshot® multiplex assay. Minor allele frequencies (MAF)were compared to representative populations of Africa, Asia and Europe, from Ensembl. MAFs for S14F, V519F, rs622342 and P341L were 2.0%, 6.0%, 6.0% and 1.0%, respectively. Sixteen of nineteen investigated non-synonymous SNPs were monomorphic. No study participant harbored variant alleles for S189L, G220V, P283L, G401S, M420V, M440I, G465R, I542V, R61C, R287G, C88S, A306T, A413V, I421F, C436F and V501E. Haplotype, CGTCGCCGCGCAAGAGGTGA, was most frequently observed (81.23%).Further investigations are encouraged to evaluate potential roles these SNPs could play in the therapeutic efficacy of clinically important drugs and in the development of various diseases in the Zulu population.

Keywords: OCT1, PCR, SNaPshot assay, Zulu population.

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1 A Novel Prediction Method for Tag SNP Selection using Genetic Algorithm based on KNN

Authors: Li-Yeh Chuang, Yu-Jen Hou, Jr., Cheng-Hong Yang

Abstract:

Single nucleotide polymorphisms (SNPs) hold much promise as a basis for disease-gene association. However, research is limited by the cost of genotyping the tremendous number of SNPs. Therefore, it is important to identify a small subset of informative SNPs, the so-called tag SNPs. This subset consists of selected SNPs of the genotypes, and accurately represents the rest of the SNPs. Furthermore, an effective evaluation method is needed to evaluate prediction accuracy of a set of tag SNPs. In this paper, a genetic algorithm (GA) is applied to tag SNP problems, and the K-nearest neighbor (K-NN) serves as a prediction method of tag SNP selection. The experimental data used was taken from the HapMap project; it consists of genotype data rather than haplotype data. The proposed method consistently identified tag SNPs with considerably better prediction accuracy than methods from the literature. At the same time, the number of tag SNPs identified was smaller than the number of tag SNPs in the other methods. The run time of the proposed method was much shorter than the run time of the SVM/STSA method when the same accuracy was reached.

Keywords: Genetic Algorithm (GA), Genotype, Single nucleotide polymorphism (SNP), tag SNPs.

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