Adel A. Alhamdan

Exploration of deleterious single nucleotide polymorphisms in late-onset Alzheimer disease susceptibility genes

Non-synonymous single nucleotide polymorphisms (nsSNPs) are considered as biomarkers to disease susceptibility. In the present study, nsSNPs in CLU, PICALM and BIN1 genes were screened for their functional impact on concerned proteins and their plausible role in Alzheimer disease (AD) susceptibility. Initially, SNPs were retrieved from dbSNP database, followed by identification of potentially deleterious nsSNPs and prediction of their effect on proteins by PolyPhen and SIFT. Protein stability and the probability of mutation occurrence were predicted using I-Mutant and PANTHER respectively. SNPs3D and FASTSNP were used for the functional analysis of nsSNPs. The functional impact on the 3D structure of proteins was evaluated by SWISSPDB viewer and NOMAD-Ref server. On analysis, 3 nsSNPs with IDs rs12800974 (T158P) of PICALM and rs11554585 (R397C) and rs11554585 (N106D) of BIN1 were predicted to be functionally significant with higher scores of I-Mutant, SIFT, PolyPhen, PANTHER, FASTSNP and SNPs3D. The mutant models of these nsSNPs also showed very high energies and RMSD values compared to their native structures. Current study proposes that the three nsSNPs identified in this study constitute a unique resource of potential genetic factors for AD susceptibility.

Screening and structural evaluation of deleterious Non-Synonymous SNPs of ePHA2 gene involved in susceptibility to cataract formation

Age-related cataract is clinically and genetically heterogeneous disorder affecting the ocular lens, and the leading cause of vision loss and blindness worldwide. Here we screened nonsynonymous single nucleotide polymorphisms (nsSNPs) of a novel gene, EPHA2 responsible for age related cataracts. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on protein was predicted by PolyPhen and SIFT respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the EPHA2 protein was evaluated by using SWISSPDB viewer and NOMAD-Ref server. Our analysis revealed 16 SNPs as nonsynonymous out of which 6 nsSNPs, namely rs11543934, rs2291806, rs1058371, rs1058370, rs79100278 and rs113882203 were found to be least stable by I-Mutant 2.0 with DDG value of > −1.0. nsSNPs, namely rs35903225, rs2291806, rs1058372, rs1058370, rs79100278 and rs113882203 showed a highly deleterious tolerance index score of 0.00 by SIFT server. Four nsSNPs namely rs11543934, rs2291806, rs1058370 and rs113882203 were found to be probably damaging with PSIC score of ≥ 2. 0 by Polyp hen server. Three nsSNPs namely, rs11543934, rs2291806 and rs1058370 were found to be highly polymorphic with a risk score of 3-4 with a possible effect of Non-conservative change and splicing regulation by FASTSNP. The total energy and RMSD value was higher for the mutant-type structure compared to the native type structure. We concluded that the nsSNP namely rs2291806 as the potential functional polymorphic that is likely to have functional impact on the EPHA2 gene.

Screening and Evaluation of Deleterious SNPs in APOE Gene of Alzheimer’s Disease

Introduction. Apolipoprotein E (APOE) is an important risk factor for Alzheimers disease (AD) and is present in 30–50% of patients who develop late-onset AD. Several single-nucleotide polymorphisms (SNPs) are present in APOE gene which act as the biomarkers for exploring the genetic basis of this disease. The objective of this study is to identify deleterious nsSNPs associated with APOE gene. Methods. The SNPs were retrieved from dbSNP. Using I-Mutant, protein stability change was calculated. The potentially functional nonsynonymous (ns) SNPs and their effect on protein was predicted by PolyPhen and SIFT, respectively. FASTSNP was used for functional analysis and estimation of risk score. The functional impact on the APOE protein was evaluated by using Swiss PDB viewer and NOMAD-Ref server. Results. Six nsSNPs were found to be least stable by I-Mutant 2.0 with DDG value of >−1.0. Four nsSNPs showed a highly deleterious tolerance index score of 0.00. Nine nsSNPs were found to be probably damaging with position-specific independent counts (PSICs) score of ≥2.0. Seven nsSNPs were found to be highly polymorphic with a risk score of 3-4. The total energies and root-mean-square deviation (RMSD) values were higher for three mutant-type structures compared to the native modeled structure. Conclusion. We concluded that three nsSNPs, namely, rs11542041, rs11542040, and rs11542034, to be potentially functional polymorphic.

Antihypertensive effect of Melothria maderaspatana leaf fractions on DOCA-salt-induced hypertensive rats and identification of compounds by GC-MS analysis.

The present study was designed to investigate the antihypertensive effect of Melothria maderaspatana leaf fractions on deoxycorticosterone acetate (DOCA)-salt-induced hypertensive rats and to identify compounds from the active fraction by GC–MS analysis. Administration of DOCA salt significantly increased the systolic and diastolic blood pressure compared to sham-operated control rats. When treated with chloroform (CFM), ethyl acetate (EAFM) or methanol fractions of M. maderaspatana (MFM), EAFM alone significantly lowered the systolic and diastolic blood pressure. The levels of magnesium and copper significantly increased in plasma and decreased in tissues while the zinc level significantly increased in plasma and tissues, and administration of EAFM brought these parameters back to sham-operated control levels. By GC–MS analysis, phytochemicals such as coumarin, vallinic acid, p-coumaric acid, gallic acid, caffeic acid, and ferulic acid were identified in EAFM. In conclusion, the EAFM controls blood pressure in DOCA-salt hypertensive rats and reverts the metabolic alterations in magnesium, copper and zinc.

The nutritional, glutathione and oxidant status of elderly subjects admitted to a university hospital.

Background/Aim: Malnutrition in elderly patients is common in hospitals, and many of the age associated chronic diseases have a common factor, which is oxidative stress. The aim of the study was to evaluate the nutritional status, glutathione, and oxidant status of elderly patients. Patients and Methods: The mini-nutritional assessment (MNA) was used to determine the nutritional status of elderly patients. Glutathione concentration in the whole blood, plasma albumin, and thiobarbituric acid-reactive substances (TBARS) levels was measured spectrophotometrically by the enzymatic recycling method. In addition, length of hospital stay was estimated. All measurements were taken within 48 h after admission. Results: The results showed that more than two-thirds of the elderly were classified as at risk of malnutrition and malnourished. About 45% and 53% elevation in the TBARS was found in at risk of being malnourished and in the malnourished groups, respectively, compared to the well-nourished group, but the elevation did not reach the significant level. No significant differences in the glutathione concentration and in the length of hospital stay were found among the three mini-nutritional assessment categories. Conclusions: The study indicated the necessity of performing the MNA test for elderly upon admission to hospitals, and more attention needs to be paid to this vulnerable group of people.

Evaluation of health care services provided for older adults in primary health care centers and its internal environment. A step towards age-friendly health centers

Objectives: To evaluate the health care services provided for older adults by primary health care centers (PHCCs) in Riyadh, Kingdom of Saudi Arabia (KSA), and the ease of use of these centers by older adults. Methods: Between October 2013 and January 2014, we conducted a descriptive cross-sectional study of 15 randomly selected PHCCs in Riyadh City, KSA. The evaluation focused on basic indicators of clinical services offered and factors indicative of the ease of use of the centers by older adults. Evaluations were based upon the age-friendly PHCCs toolkit of the World Health Organization. Results: Coverage of basic health assessments (such as blood pressure, diabetes, and blood cholesterol) was generally good. However, fewer than half of the PHCCs offered annual comprehensive screening for the common age-related conditions. There was no screening for cancer. Counseling on improving lifestyle was provided by most centers. However, there was no standard protocol for counseling. Coverage of common vaccinations was poor. The layout of most PHCCs and their signage were good, except for lack of Braille signage. There may be issues of access of older adults to PHCCs through lack of public transport, limited parking opportunities, the presence of steps, ramps, and internal stairs, and the lack of handrails. Conclusions: Clinical services and the internal environment of PHCCs can be improved. The data will be useful for health-policy makers to improve PHCCs to be more age-friendly.

Evaluation and identification of damaged single nucleotide polymorphisms in COL1A1 gene involved in osteoporosis

Introduction Single-nucleotide polymorphisms (SNPs) are biomarkers for exploring the genetic basis of many complex human diseases. The prediction of SNPs is promising in modern genetic analysis but it is still a great challenge to identify the functional SNPs in a disease-related gene. The computational approach has overcome this challenge and an increase in the successful rate of genetic association studies and reduced cost of genotyping have been achieved. The objective of this study is to identify deleterious non-synonymous SNPs (nsSNPs) associated with the COL1A1 gene. Material and methods The SNPs were retrieved from the Single Nucleotide Polymorphism Database (dbSNP). Using I-Mutant, protein stability change was calculated. The potentially functional nsSNPs and their effect on proteins were predicted by PolyPhen and SIFT respectively. FASTSNP was used for estimation of risk score. Results Our analysis revealed 247 SNPs as non-synonymous, out of which 5 nsSNPs were found to be least stable by I-Mutant 2.0 with a DDG value of > –1.0. Four nsSNPs, namely rs17853657, rs17857117, rs57377812 and rs1059454, showed a highly deleterious tolerance index score of 0.00 with a change in their physicochemical properties by the SIFT server. Seven nsSNPs, namely rs1059454, rs8179178, rs17853657, rs17857117, rs72656340, rs72656344 and rs72656351, were found to be probably damaging with a PSIC score difference between 2.0 and 3.5 by the PolyPhen server. Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, were found to be highly polymorphic with a risk score of 3-4 with a possible effect of non-conservative change and splicing regulation by FASTSNP. Conclusions Three nsSNPs, namely rs1059454, rs17853657 and rs17857117, are potential functional polymorphisms that are likely to have a functional impact on the COL1A1 gene.

Analysis of the Inhibitory Effect of Flavonoids on H-Ras Protein: An Anticancer Drug Target

Background: GTP-bound mutant forms of H-Ras (Harvey-Ras) proteins are found in almost 30% of human tumors. In the present in silico study, the inhibitory effect of different flavonoid compounds on mutant H-Ras protein p21 has been assessed. The inhibitory effect of flavonoids is compared with three known clinical anticancer drugs. Besides, these have been interacted with normal H-Ras and tumor necrosis factor (TNF) proteins for toxicity check. Results: Upon docking, it was found that flavonoids such as naringenin, daidzein, and hesperetin showed highest affinity (most negative ΔG), while rutin showed no affinity towards mutant H-Ras. The three clinical anticancer agents (erlotinib, letrozole and exemestane) showed binding energies in the range of –1.11 to –5.51 kcal/mol which is comparatively lower than the flavonoids indicating efficacy of flavonoids to prevent complex formation with Raf and thereby prevent downstream effects. However, flavonoids showed no interaction with normal H-Ras and TNF indicating little or no cytotoxicity. Conclusion: Our study demonstrates that flavonoids (naringenin, daidzein, and hesperetin) are effective drugs to inhibit complex formation between mutant H-Ras P21 and RBD of Raf.

4th Congress of the International Society of Nutrigenetics/Nutrigenomics (ISNN)

1 pagina. 4th Congress of the International Society of Nutrigenetics/Nutrigenomics (ISNN) (Pamplona, Spain, 18-20 november, 2010)