May N. Al-Muammar

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.

Predictors of physicians’ practices related to nutritional counseling and management in Riyadh City

Abstract Background A growing interest has become increasing in the role of physicians as effective resources for the promotion of good nutritional practices, however, the factors that impede their nutritional counseling and management practice (NC&M) are not clearly understood in Saudi Arabia. Objectives The objectives of the study were to investigate physicians’ practices concerning NC&M and to explore some determinants that predict such practices. Results Data of 266 physicians working in big hospitals in Riyadh showed that only 7.9% of the respondents reported that they were practicing all aspects of NC&M; including nutritional assessment, therapy, and education. Those who practiced any one of these aspects ranged between 13.9–40.2%, meanwhile, 28% frankly reported that they did not practice NC&M. In the last year, the mean percentage of patients placed on nutrition therapy was 24.15 ± 27.78% and the mean percentage of clinic time dedicated to NC&M was 21.49 ± 20.54%. Most of the respondents (72.9%) had poor nutritional knowledge score. Overall, 19.2% previously attended CME in nutrition. Only 1.5% and 28.6% self-assessed themselves as “outstanding” and “good” in NC&M skills and the mean total self-efficacy in NC&M was moderate. The majority (77.8%) perceived NC&M as highly or moderately relevant to their specialties. Physicians attitude and perceived efficacy towards NC&M was moderately high as the mean scores were greater than their midpoint. Their perceived barriers of NC&M were considerably moderate; as the mean total score was found to be near the midpoint of that scale. Among the seven independent variables entered the binary logistic regression of physicians practice of NC&M, only the knowledge, attitude, and self-efficacy scores were significantly associated with their NC&M practice. These three predictors contributed by 23.5% of the variation of physician practice of NC&M. Conclusions Physicians knowledge, self-efficacy, attitudes and other factors should be stressed in any intervention warranted to improve their nutritional practices.

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.