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.
Abstract: As genetic diversity is most important for existing, breeding and production of any fish; this study was undertaken for investigating genetic diversity of freshwater mud eel, Monopterus cuchia at population level where three ecological populations such as flooded area of Sylhet (P1), open water of Moulvibazar (P2) and open water of Sunamganj (P3) districts of Bangladesh were considered. Four arbitrary RAPD primers (OPB-12, C0-4, B-03 and OPB-08) were screened and RAPD banding patterns were analyzed among the populations considering 15 individuals of each population. In total 174, 138 and 149 bands were detected in the populations of P1, P2 and P3 respectively; however, each primer revealed less number of bands in each population. 100% polymorphic loci were recorded in P2 and P3 whereas only one monomorphic locus was observed in P1, recorded 97.5% polymorphism. Different genetic parameters such as inter-individual pairwise similarity, genetic distance, Nei genetic similarity, linkage distances, cluster analysis and allelic information, etc. were considered for measuring genetic diversity. The average inter-individual pairwise similarity was recorded 2.98, 1.47 and 1.35 in P1, P2 and P3 respectively. Considering genetic distance analysis, the highest distance 1 was recorded in P2 and P3 and the lowest genetic distance 0.444 was found in P2. The average Nei genetic similarity was observed 0.19, 0.16 and 0.13 in P1, P2 and P3, respectively; however, the average linkage distance was recorded 24.92, 17.14 and 15.28 in P1, P3 and P2 respectively. Based on linkage distance, genetic clusters were generated in three populations where 6 clades and 7 clusters were found in P1, 3 clades and 5 clusters were observed in P2 and 4 clades and 7 clusters were detected in P3. In addition, allelic information was observed where the frequency of p and q alleles were observed 0.093 and 0.907 in P1, 0.076 and 0.924 in P2, 0.074 and 0.926 in P3 respectively. The average gene diversity was observed highest in P2 (0.132) followed by P3 (0.131) and P1 (0.121) respectively.
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.
Abstract: Osteoporosis is a common multifactorial disease with
a strong genetic component characterized by reduced bone mass and
increased risk of fractures. Genetic factors play an important role in
the pathogenesis of osteoporosis. The aim of our study was to
identify the genotype and allele distribution of T245G polymorphism
in OPG gene in Slovak postmenopausal women. A total of 200
unrelated Slovak postmenopausal women with diagnosed
osteoporosis and 200 normal controls were genotyped for T245G
(rs3134069) polymorphism of OPG gene. Genotyping was performed
using the Custom Taqman®SNP Genotyping assays. Genotypes and
alleles frequencies showed no significant differences (p=0.5551;
p=0.6022). The results of the present study confirm the importance of
T245G polymorphism in OPG gene in the pathogenesis of
osteoporosis.
Abstract: Osteoporosis is a complex health disease characterized by low bone mineral density, which is determined by an interaction of genetics with metabolic and environmental factors. Current research in genetics of osteoporosis is focused on identification of responsible genes and polymorphisms. TNFRSF11B gene plays a key role in bone remodeling. The aim of this study was to investigate the genotype and allele distribution of A163G (rs3102735) osteoprotegerin gene promoter and G1181C (rs2073618) osteoprotegerin first exon polymorphisms in the group of 180 unrelated postmenopausal women with diagnosed osteoporosis and 180 normal controls. Genomic DNA was isolated from peripheral blood leukocytes using standard methodology. Genotyping for presence of different polymorphisms was performed using the Custom Taqman®SNP Genotyping assays. Hardy-Weinberg equilibrium was tested for each SNP in the groups of participants using the chi-square (χ2) test. The distribution of investigated genotypes in the group of patients with osteoporosis were as follows: AA (66.7%), AG (32.2%), GG (1.1%) for A163G polymorphism; GG (19.4%), CG (44.4%), CC (36.1%) for G1181C polymorphism. The distribution of genotypes in normal controls were follows: AA (71.1%), AG (26.1%), GG (2.8%) for A163G polymorphism; GG (22.2%), CG (48.9%), CC (28.9%) for G1181C polymorphism. In A163G polymorphism the variant G allele was more common among patients with osteoporosis: 17.2% versus 15.8% in normal controls. Also, in G1181C polymorphism the phenomenon of more frequent occurrence of C allele in the group of patients with osteoporosis was observed (58.3% versus 53.3%). Genotype and allele distributions showed no significant differences (A163G: χ2=0.270, p=0.605; χ2=0.250, p=0.616; G1181C: χ2= 1.730, p=0.188; χ2=1.820, p=0.177). Our results represents an initial study, further studies of more numerous file and associations studies will be carried out. Knowing the distribution of genotypes is important for assessing the impact of these polymorphisms on various parameters associated with osteoporosis. Screening for identification of “at-risk” women likely to develop osteoporosis and initiating subsequent early intervention appears to be most effective strategy to substantially reduce the risks of osteoporosis.
Abstract: Metrics is the process by which numbers or symbols
are assigned to attributes of entities in the real world in such a way as
to describe them according to clearly defined rules. Software metrics
are instruments or ways to measuring all the aspect of software
product. These metrics are used throughout a software project to
assist in estimation, quality control, productivity assessment, and
project control. Object oriented software metrics focus on
measurements that are applied to the class and other characteristics.
These measurements convey the software engineer to the behavior of
the software and how changes can be made that will reduce
complexity and improve the continuing capability of the software.
Object oriented software metric can be classified in two types static
and dynamic. Static metrics are concerned with all the aspects of
measuring by static analysis of software and dynamic metrics are
concerned with all the measuring aspect of the software at run time.
Major work done before, was focusing on static metric. Also some
work has been done in the field of dynamic nature of the software
measurements. But research in this area is demanding for more work.
In this paper we give a set of dynamic metrics specifically for
polymorphism in object oriented system.
Abstract: Type 2 diabetes mellitus (T2DM) is a complex
metabolic disorder that characterized by the presence of high glucose
in blood that cause from insulin resistance and insufficiency due to
deterioration β-cell Langerhans functions. T2DM is commonly
caused by the combination of inherited genetic variations as well as
our own lifestyle. Metallothionein (MT) is a known cysteine-rich
protein responsible in helping zinc homeostasis which is important in
insulin signaling and secretion as well as protection our body from
reactive oxygen species (ROS). MT scavenged ROS and free
radicals in our body happen to be one of the reasons of T2DM and its
complications. The objective of this study was to investigate the
association of MT1A and MT2A polymorphisms between T2DM and
control subjects among Malay populations. This study involved 150
T2DM and 120 Healthy individuals of Malay ethnic with mixed
genders. The genomic DNA was extracted from buccal cells and
amplified for MT1A and MT2A loci; the 347bp and 238bp banding
patterns were respectively produced by mean of the Polymerase
Chain Reaction (PCR). The PCR products were digested with Mlucl
and Tsp451 restriction enzymes respectively and producing
fragments lengths of (158/189/347bp) and (103/135/238bp)
respectively. The ANOVA test was conducted and it shown that there
was a significant difference between diabetic and control subjects for
age, BMI, WHR, SBP, FPG, HBA1C, LDL, TG, TC and family
history with (P0.05). The genotype
frequency for AA, AG and GG of MT1A polymorphisms was 72.7%,
22.7% and 4.7% in cases and 15%, 55% and 30% in control
respectively. As for MT2A, genotype frequency of GG, GC and CC
was 42.7%, 27.3% and 30% in case and 5%, 40% and 55% for
control respectively. Both polymorphisms show significant difference
between two investigated groups with (P=0.000). The Post hoc test
was conducted and shows a significant difference between the
genotypes within each polymorphism (P=0. 000). The MT1A and
MT2A polymorphisms were believed to be the reliable molecular
markers to distinguish the T2DM subjects from healthy individuals in
Malay populations.
Abstract: The utility of expert system generators has been
widely recognized in many applications. Several generators based on
concept of the paradigm object, have been recently proposed. The
generator of oriented object expert system (GSEOO) offers
languages that are often complex and difficult to use. We propose in
this paper an extension of the expert system generator, JESS, which
permits a friendly use of this expert system. The new tool, called
VISUAL JESS, bring two main improvements to JESS. The first
improvement concerns the easiness of its utilization while giving
back transparency to the syntax and semantic aspects of the JESS
programming language. The second improvement permits an easy
access and modification of the JESS knowledge basis. The
implementation of VISUAL JESS is made so that it is extensible and
portable.