Mapping genetic research in non-communicable disease publications in selected Arab countries: first step towards a guided research agenda.

BACKGROUND: In the Arab world, intervention and policy response to non-communicable diseases (NCD) has been weak despite extensive epidemiological evidence highlighting the alarmingly increased prevalence of chronic diseases. Generating genetic information is one key component to promote efficient disease management strategies. This study undertook a scoping review to generate the profile of the undertaken research on genetics of NCD publications in selected Arab countries. An analysis of the research produced examined the extent, range, nature, topic and methods of published research. The study aimed at identifying the gaps in genetic NCD research to inform policy action for NCD prevention and control. METHODS: The scoping review was conducted based on the five-stage methodological framework and included countries in Arab region selected to represent various economies and epidemiological transitions. RESULTS: The search identified 555 articles that focus on genetics-NCD research in the selected Arab countries over the duration of this study (January 2000 to December 2013). The most commonly conducted research was descriptive and clinically focused, rather than etiologically focused. Country-specific carrier and risk screening studies were not among the top research designs. The genetic component of certain highly heritable diseases, as well as diabetes, obesity, hypertension, chronic lung dysfunction and metabolic syndrome were all under investigated. CONCLUSIONS: This scoping review identified gaps for further research in the context of bioinformatics and genome-wide association studies. Genetic research in the Arab region has to be redirected towards NCDs with the highest morbidity, heritability and health burden within each country. A focused research plan to include community genetics is required for its proper integration in the Arab community

Descriptive analysis of NCD papers published from 2000 until 2013 in selected Arab countries.

<p>Descriptive analysis of NCD papers published from 2000 until 2013 in selected Arab countries.</p

Genetic literacy among primary care physicians in a resource-constrained setting

Abstract Background Genetic literacy among primary healthcare providers is crucial for appropriate patient care with the advances in genetic and genomic medicine. Studies from high-income countries highlight the lack of knowledge in genetics and the need to develop curricula for continuing professional development of non-geneticists. Scarce data is available from resource-constrained countries in Middle East and North Africa. Lebanon is a small country in this region characterized by high rates of consanguinity and genetic disorders like several surrounding countries, such as Jordan, Syria, and Turkey. Methods The primary aim of this study assessed the genetic literacy, self-perceived and actual knowledge as well as practices among primary care providers in Lebanon. The secondary aim identified their educational needs and proposed evidence-based continuing education programs. A cross-sectional survey-based study, using a self-administered questionnaire, was conducted targeting physicians from Family Medicine, Obstetrics and Gynecology, and Pediatrics. The questionnaire was divided into five sections: demographics, familiarity with genetic tests, self-reported and actual knowledge, genetic practices, and educational needs. Statistics were performed using SPSS v24. The Chi-square test was used for independent variables. Differences between mean scores were measured using paired sample t-tests for groups of two levels and one-way ANOVA for more than two. Multiple linear regression was used to study the variables associated with the knowledge score while controlling for other variables. Results The survey included 123 physicians. They were mostly familiar with karyotype as first-tier genetic test. Although 38% perceived their knowledge as good, only 6% scored as such in knowledge assessment. A better knowledge score was observed in academic institutions as well as in urban settings (p<0.05). One third never ordered any genetic testing, mostly due to poor knowledge. Almost all (98%) were ready to attend continuing professional development sessions in genetics. Conclusion Our findings show the need to improve genetic literacy among healthcare frontliners, focusing on remote regions and nonacademic centers in Lebanon, a model for other resource-constrained country in the Middle East and North Africa region. This study advances recommendations for evidence-based genetic continuing education programs and highlighted the role of that the few genetic specialists can play in their successful implementation

El Diario de Pontevedra : periódico liberal: Ano XXXIII Número 9637 - 1916 xuño 3

<p><b>Time trends in NCD publication rate between 2000 and 2013, by (a) country and (b) study type*.</b> *Slopes (regression coefficients) are presented in parentheses</p

Resistance to diet-induced obesity in mice with a single substituted chromosome

Obesity and its comorbidities are taking an increasing toll on human health. Key pathways that were identified with single gene variants in humans and model organisms have led to improved understanding and treatment of rare cases of human obesity. However, similar progress remains elusive for the more common multifactorial cases of metabolic dysfunction and disease. A survey of mouse chromosome substitution strains (CSSs) provided insight into the complex genetic control of diet-induced obesity and related conditions. We now report a survey of 60 traits related to obesity and metabolic syndrome in mice with a single substituted chromosome as well as selected traits measured in congenic strains derived from the substituted strain. We found that each strain that was resistant to diet-induced obesity had a distinct phenotype that uniquely modeled different combinations of traits related to metabolic disease. For example, the chromosome 6 CSS remained insulin resistant in the absence of obesity, demonstrating an atypical relationship between body weight and insulin resistance. These results provide insights into the genetic control of constant components of this mouse model of diet-induced metabolic disease as well as phenotypes that vary depending on genetic background. A better understanding of these genotype-phenotype relationships may enable a more individualized diagnosis and treatment of obesity and the metabolic syndrome

Over- or under-representation of the four major NCDs in the literature compared to proportionate mortality rates (countries presented in order of increasing gaps).

<p>(Data on proportionate mortality was sourced from <a href="http://apps.who.int/gho/data/node.main.A864?lang=en" target="_blank">http://apps.who.int/gho/data/node.main.A864?lang=en</a> for all countries except Palestine, for which data was retrieved from the Occupied Palestinian territory STEPS survey 2010–2011. <a href="http://www.emro.who.int/pse/programmes/ncds-pal.html" target="_blank">http://www.emro.who.int/pse/programmes/ncds-pal.html</a>, <a href="http://www.abudis.net/chronic_diseases_in_palestine.htm" target="_blank">http://www.abudis.net/chronic_diseases_in_palestine.htm</a>)</p

SLC35B4, an Inhibitor of Gluconeogenesis, Responds to Glucose Stimulation and Downregulates Hsp60 among Other Proteins in HepG2 Liver Cell Lines

SLC35B4, solute receptor for UDP-N-acetylglucosamine and UDP-xylose, is associated with diabetes and predisposing conditions. This study investigated the localization of SLC35B4 and compared the differential expression between a knockdown of SLC35B4 and controls in HepG2. Responsiveness to glucose, expression, and localization were assayed using Western blot and immunostaining. Localization was confirmed using a proximity ligation assay. Two-dimensional (2D) gel electrophoresis and MALDI-TOF were used to identify differentially expressed proteins and pathway analysis was performed. SLC35B4 was increased by 60% upon glucose stimulation and localized in Golgi apparatus and endoplasmic reticulum. Presence of SLC35B4 in the Golgi apparatus suggests its involvement in the biosynthesis of glycoconjugate proteins. Four proteins were markedly under-expressed (Hsp60, HspA8, TUBA1A, and ENO1) and linked to the pathogenesis of diabetes or post-translationally modified by O-GlcNAc. Glucose levels activate SLC35B4 expression. This triggers a downstream effect via Hsp60 and other proteins. We hypothesize that the downstream effect on the proteins is mediated via altering the glycosylation pattern inside liver cells. The downstream cascade ultimately alters the ability of cultured liver cells to inhibit endogenous glucose production, and this could play a role in the association of the above-listed genes with the pathogenesis of diabetes

Trend in quantity (number of publications per year) of NCD reports in selected Arab countries between 2000–2013.

<p>Trend in quantity (number of publications per year) of NCD reports in selected Arab countries between 2000–2013.</p

Deep congenic analysis identifies many strong, context-dependent QTLs, one of which, Slc35b4, regulates obesity and glucose homeostasis

Although central to many studies of phenotypic variation and disease susceptibility, characterizing the genetic architecture of complex traits has been unexpectedly difficult. For example, most of the susceptibility genes that contribute to highly heritable conditions such as obesity and type 2 diabetes (T2D) remain to be identified despite intensive study. We took advantage of mouse models of diet-induced metabolic disease in chromosome substitution strains (CSSs) both to characterize the genetic architecture of diet-induced obesity and glucose homeostasis and to test the feasibility of gene discovery. Beginning with a survey of CSSs, followed with genetic and phenotypic analysis of congenic, subcongenic, and subsubcongenic strains, we identified a remarkable number of closely linked, phenotypically heterogeneous quantitative trait loci (QTLs) on mouse chromosome 6 that have unexpectedly large phenotypic effects. Although fine-mapping reduced the genomic intervals and gene content of these QTLs over 3000-fold, the average phenotypic effect on body weight was reduced less than threefold, highlighting the “fractal” nature of genetic architecture in mice. Despite this genetic complexity, we found evidence for 14 QTLs in only 32 recombination events in less than 3000 mice, and with an average of four genes located within the three body weight QTLs in the subsubcongenic strains. For Obrq2a1, genetic and functional studies collectively identified the solute receptor Slc35b4 as a regulator of obesity, insulin resistance, and gluconeogenesis. This work demonstrated the unique power of CSSs as a platform for studying complex genetic traits and identifying QTLs