Genetics of Inborn Errors of Immunity in highly consanguineous Middle Eastern and North African populations.

Consanguineous marriages in Middle Eastern and North African (MENA) countries are deeply-rooted tradition and highly prevalent resulting into increased prevalence of autosomal recessive diseases including Inborn Errors of Immunity (IEIs). Molecular genetic testing is an important diagnostic tool for IEIs since it provides a definite diagnosis, genotype-phenotype correlation, and guide therapy. In this review, we will discuss the current state and challenges of genomic and variome studies in MENA region populations, as well as the importance of funding advanced genome projects. In addition, we will review the MENA underlying molecular genetic defects of over 2457 patients published with the common IEIs, where autosomal recessive mode of inheritance accounts for 76% of cases with increased prevalence of combined immunodeficiency diseases (50%). The efforts made in the last three decades in terms of international collaboration and of in situ capacity building in MENA region countries led to the discovery of more than 150 novel genes involved in IEIs. Expanding sequencing studies within the MENA will undoubtedly be a unique asset for the IEI genetics which can advance research, and support precise genomic diagnostics and therapeutics.

The Impact of Recent Demography on Functional Genetic Variation in North African Human Groups.

The strategic location of North Africa has made the region the core of a wide range of human demographic events, including migrations, bottlenecks, and admixture processes. This has led to a complex and heterogeneous genetic and cultural landscape, which remains poorly studied compared to other world regions. Whole-exome sequencing is particularly relevant to determine the effects of these demographic events on current-day North Africans' genomes, since it allows to focus on those parts of the genome that are more likely to have direct biomedical consequences. Whole-exome sequencing can also be used to assess the effect of recent demography in functional genetic variation and the efficacy of natural selection, a long-lasting debate. In the present work, we use newly generated whole-exome sequencing and genome-wide array genotypes to investigate the effect of demography in functional variation in 7 North African populations, considering both cultural and demographic differences and with a special focus on Amazigh (plur. Imazighen) groups. We detect genetic differences among populations related to their degree of isolation and the presence of bottlenecks in their recent history. We find differences in the functional part of the genome that suggest a relaxation of purifying selection in the more isolated groups, allowing for an increase of putatively damaging variation. Our results also show a shift in mutational load coinciding with major demographic events in the region and reveal differences within and between cultural and geographic groups.

Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management. METHODS: A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique. RESULTS: The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p > 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking. CONCLUSION: In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

A new primate community from the earliest Oligocene of the Atlantic margin of Northwest Africa: Systematic, paleobiogeographic, and paleoenvironmental implications.

We report a new Paleogene primate community discovered in the uppermost part of the Samlat Formation outcropping on the continental shore of the Rio de Oro, east of the Dakhla peninsula (in the south of Morocco, near the northern border of Mauritania). Fossils consist of isolated teeth, which were extracted by wet screening of estuarine sediments (DAK C2) dating from the earliest Oligocene (ca. 33.5 Ma). These dental remains testify to the presence of at least eight primate species, documenting distinct families, four of which are among the Anthropoidea (Oligopithecidae [Catopithecus aff. browni], Propliopithecidae [?Propliopithecus sp.], Parapithecidae [Abuqatrania cf. basiodontos], and Afrotarsiidae [Afrotarsius sp.]) and four in the Strepsirrhini (a Djebelemuridae [cf. 'Anchomomys' milleri], a Galagidae [Wadilemur cf. elegans], a possible lorisiform [Orogalago saintexuperyi gen. et sp. nov.], and a strepsirrhine of indeterminate affinities [Orolemur mermozi gen. et sp. nov.]). This record of various primates at Dakhla represents the first Oligocene primate community from Northwest Africa, especially from the Atlantic margin of that landmass. Considering primates plus rodents (especially hystricognaths), the taxonomic proximity at the generic (even specific) level between DAK C2 (Dakhla) and the famous Egyptian fossil-bearing localities of the Jebel Qatrani Formation (Fayum Depression), either dating from the latest Eocene (L-41) or from the early Oligocene, suggests the existence of an east-west 'trans-North African' environmental continuum during the latest Eocene-earliest Oligocene time interval. The particularly diverse mammal fauna from DAK C2, recorded within the time window of global climate deterioration characterizing the Eocene/Oligocene transition, suggests that this tropical region of northwest Africa was seemingly less affected, if at all, by the cooling and associated paleoenvironmental and biotic changes documented at that time or at least that the effects were delayed. The expected densely forested paleoenvironment bordering the western margin of North Africa at the beginning of the early Oligocene probably offered better tropical refugia than higher latitudes or more inland areas during the cooling episode.

Prevalence of metabolic dysfunction-associated steatotic liver disease in the Middle East and North Africa.

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD), is common and closely associated with type 2 diabetes (T2D). We assessed the prevalence of NAFLD/MASLD in the general population and among patients with T2D in the Middle East and North Africa (MENA) region. METHODS: We searched PubMed and Embase for English-language articles published between 1990 and 2023 according to PRISMA. Each country's NAFLD/MASLD prevalence in the general population and in T2D patients was predicted by using a multivariable meta regression model. Input data were extracted from our systematic review, GBD and NCD Risk Factor Collaboration. Confidence intervals were constructed by using prediction intervals with the delta method. RESULTS: Meta-analytic pooling estimated the prevalence of NAFLD/MASLD as 39.43% in the general population and 68.71% among T2D patients. NAFLD/MASLD prevalence has increased from 35.42% (2008-2016) to 46.20% (2017-2020). Using GBD-2019 dataset, it was predicted that there are 141.51 million cases of NAFLD/MASLD in the MENA region. The highest number of NAFLD/MASLD cases were expected in Egypt (25.71 million), followed by Türkiye (23.33 million) and Iran (19.85 million). Estimated NAFLD prevalence exceeded 40% in 10 of 21 countries with the top countries being Kuwait (45.37%), Egypt (45.0%), Qatar (44.4%), and Jordan (43.3%). Furthermore, it was predicted that there are 24.96 million cases of NAFLD/MASLD with T2D in the MENA region. CONCLUSIONS: In the MENA region, prevalence of NAFLD/MASLD is very high and growing, necessitating an urgent need for regional public policy to deal with this growing burden.

Promoting diversity in geoheritage evaluation: creating an evaluation method for the scientific value of Quaternary sites in arid environments.

A rigorous assessment is an essential part of geoconservation, and choosing an appropriate evaluation method is essential for this process. Globally, an increasing number of sites are being assessed for their geoheritage values, but the most popular methods have been created by researchers with experiences centred in Europe, without considerations of regional differences. To understand whether regional perspectives are required in the evaluation process, this study developed a new method targeting the scientific value of Quaternary geoheritage sites in arid environments, using input from 49 researchers in geosciences and related disciplines with interests in arid landscapes. The results demonstrated the need for a new or modified method, given the different preferences in the weighting system and the necessity to include additional criteria specific to the type of sites targeted by the study. The strong preference to include a new criterion on connections with archaeology/anthropology highlighted the significance of the interdisciplinary scientific values of Quaternary geoheritage sites in arid environments. These findings imply the need for regional diversity or adjustments in geoheritage evaluation. Future research is required to consider such differences for geoheritage values beyond the scientific dimension, such as educational values and touristic values in diverse geographical settings. This article is part of the Theo Murphy meeting issue 'Geodiversity for science and society'.

Epidemiology and outcomes of pediatric autosomal recessive polycystic kidney disease in the Middle East and North Africa.

The incidence of rare diseases is expected to be comparatively higher in the Middle East and North Africa (MENA) region than in other parts of the world, attributed to the high prevalence of consanguinity. Most MENA countries share social and economic statuses, cultural relativism, religious beliefs, and healthcare policies. Polycystic kidney diseases (PKDs) are the most common genetic causes of kidney failure, accounting for nearly 8.0% of dialysis cases. The development of PKDs is linked to variants in several genes, including PKD1, PKD2, PKHD1, DZIP1L, and CYS1. Autosomal recessive PKD (ARPKD) is the less common yet aggressive form of PKD. ARPKD has an estimated incidence between 1:10,000 and 1:40,000. Most patients with ARPKD require kidney replacement therapy earlier than patients with autosomal dominant polycystic kidney disease (ADPKD), often in their early years of life. This review gathered data from published research studies and reviews of ARPKD, highlighting the epidemiology, phenotypic presentation, investigations, genetic analysis, outcomes, and management. Although limited data are available, the published literature suggests that the incidence of ARPKD may be higher in the MENA region due to consanguineous marriages. Patients with ARPKD from the MENA region usually present at a later disease stage and have a relatively short time to progress to kidney failure. Limited data are available regarding the management practice in the region, which warrants further investigations.

The burden of dermatitis from 1990-2019 in the Middle East and North Africa region.

BACKGROUND: There are several types of dermatitis, each capable of causing enduring changes that extend beyond physical discomfort. In severe cases, dermatitis can significantly affect mental health, social interactions, and the overall quality of life. This study reports the burden of dermatitis in the Middle East and North Africa (MENA) region from 1990 to 2019, according to sex, age category, and socio-demographic index (SDI). METHODS: Publicly available data regarding the point prevalence, incidence, and years lived with disability (YLDs) were collected from the Global Burden of Disease 2019 study for both the MENA region and its constituent countries. The point prevalence, incidence, and YLDs of dermatitis were represented as counts and age-standardised rates with 95% uncertainty intervals (UIs). RESULTS: In 2019, the age-standardised point prevalence of dermatitis was 2744.6 (2517.8-3003.1) per 100,000 population, which was 2.3% lower than in 1990. The YLD rate was 92.3 (55.6-143.4) per 100,000 population, which was 3.1% lower than in 1990. The largest point prevalence rates were observed among those aged 70-74, for both sexes. The 2019 MENA/Global DALY ratio was not above one in any age group for either sex. During the period 1990 to 2019, there was no clear correlation between the burden of dermatitis and the SDI level. CONCLUSION: The dermatitis burden in the MENA region remained relatively stable from 1990 to 2019. Future prevention efforts should focus on improving healthcare access, health education, and workplace safety regulations.

Modifiable risk factors for cancer in the middle East and North Africa: a scoping review.

PURPOSE: This scoping review examines controllable predisposing factors attributable to cancer in the Middle East and North Africa (MENA) region's adult population, highlighting opportunities to enhance cancer prevention programs. DESIGN: We systematically searched the PubMed, Science Direct, and CINAHL, EMBASE, and Cochrane Library databases from 1997 to 2022 for articles reporting on the impact of modifiable risk factors on adult patients with cancer in the MENA region. RESULTS: The review identified 42 relevant articles, revealing that tobacco consumption, obesity, physical inactivity, and diet are significant modifiable risk factors for cancer in the region. Tobacco smoking is a leading cause of lung, bladder, squamous cell carcinoma, and colorectal cancer. A shift towards a westernized, calorie-dense diet has been observed, with some evidence suggesting that a Mediterranean diet may be protective against cancer. Obesity is a known risk factor for cancer, particularly breast malignancy, but further research is needed to determine its impact in the MENA region. Physical inactivity has been linked to colorectal cancer, but more studies are required to establish this relationship conclusively. Alcohol consumption, infections, and exposure to environmental carcinogens are additional risk factors, although the literature on these topics is limited. CONCLUSION: The review emphasizes the need for further research and the development of targeted cancer prevention strategies in the MENA region.

Burden of colorectal cancer and its risk factors in the North Africa and Middle East (NAME) region, 1990-2019: a systematic analysis of the global burden of disease study.

OBJECTIVE: The geographical differences in incidence rates of colorectal cancer (CRC) and its burden due to modifiable risk factors warrant investigating the CRC burden and its risk factors in different regions. In the current study, we aimed to estimate the burden of CRC and the share of its risk factors in the North Africa and Middle East (NAME), from 1990 to 2019. STUDY DESIGN: Systematic review. METHODS: The rates of incidence, prevalence, death, years of life lost (YLL), years lived with disability (YLD), and disability adjusted life years (DALYs) of CRC were estimated through the framework of the Global Burden of Diseases (GBD), Injuries and Risk Factors Study 2019 by age, sex, between 1990 and 2019. The CRC-related DALYs attributable to each lifestyle and metabolic risk factor was also estimated through a comparative risk assessment approach. RESULTS: In NAME region, the trends of incidence, prevalence, death, YLL, YLD, and DALYs of CRC were increasing, with higher rates in males than females over this period. High and high-middle socio-demographic index (SDI) countries had greater CRC DALYs rate compared with middle- and low-SDI countries in 2019, except for Palestine [434.66 (95% UI: 368.82, 503.88)]. In NAME region, like the global, dietary risk (33.18%), low whole grain intake (19.79%), and low intake of milk (15.77%) were the major contributing risk factors to DALYs due to CRC in 2019. CONCLUSIONS: Due to increasing trend of CRC burden and the considerable role of lifestyle and metabolic factors in its burden in NAME region, implementing fundamental strategies to minimize CRC burden and its risk factors is imperative.

Behind the scenes of research ethics committee oversight: a qualitative research study with committee chairs in the Middle East and North Africa region.

BACKGROUND: Research cites shortcomings and challenges facing research ethics committees in many regions across the world including Arab countries. This paper presents findings from qualitative in-depth interviews with research ethics committee (REC) chairs to explore their views on the challenges they face in their work with the oversight of research involving human populations. METHODS: Virtual in-depth interviews were conducted with chairs (n = 11) from both biomedical and/or social-behavioral research ethics committees in six countries, transcribed, coded and subject to thematic analysis for recurring themes. RESULTS: Two sets of recurring themes impede the work of the committees and pose concerns for the quality of the research applications: (1) procedures and committee level challenges such as heavy workload, variations in member qualification, impeding bureaucratic procedures, member overwork, and intersecting socio-cultural values in the review process; (2) inconsistencies in the researchers' competence in both applied research ethics and research methodology as revealed by their applications. CONCLUSIONS: Narratives of REC chairs are important to shed light on experiences and issues that are not captured in surveys, adding to the body of knowledge with implications for the region, and low- and middle-income countries (LMICs) in other parts of the world. International research collaborations could benefit from the findings.

Advancing Kawasaki Disease Research in the Arab World: Scoping Literature Review Analysis with Emphasis on Giant Coronary Aneurysms.

To evaluate giant aneurysms (GiAn) prevalence in Arab countries and examine contributing factors; and to review Kawasaki disease (KD) publication trends and collaborations among Arab nations. A scoping literature review was conducted to analyze the publications across the Arab world, spanning 16 countries from 1978 to 2023. The collected articles were a combination of database search with a call on Kawasaki Disease Arab Initiative (Kawarabi) members to share non-PubMed publications. Over 45 years, 50 articles originated from the Arab Countries with a 30% average annual growth rate in KD research output. Publications were evenly split between case reports (42%) and institutional series (52%). Research productivity lagged in developing nations with UAE, KSA and Egypt, contributed to 64% of total publications. Among 26 institutional series, 256 coronary artery aneurysms (CAA) from a total of 1264 KD cases were reported. Of those, 25 CAA were GiAn (prevalence 1.43% [range 0-12.5%]). The initial KD misdiagnosis rate was 4%, and incomplete KD (iKD) averaged 10.6%. Series (38.5%) that did not report iKD correlated with a higher prevalence of CAA, but not of GiAn. Longer fever duration emerged as a pivotal factor for GiAn (OR 5.06, 95%CI 1.51-17). This review unveils the research landscape of KD in the Arab world over 45 years. Initial misdiagnosis, untreated cases, delayed diagnosis and underreporting of iKD are contributing factors for an underestimated epidemiology, explaining the higher GiAn prevalence. This calls for strategic interventions to enhance KD research in these countries, aligning with Kawarabi's mission.

Prevalence and factors associated with falls in older adults in a Middle Eastern population: a retrospective cross-sectional study.

OBJECTIVE: The main objective was to determine the prevalence of falls and associated factors in older adults living in Qatar. STUDY DESIGN: Cross-sectional study. METHODS: This is a cross-sectional study of older adults aged ≥60 years with at least one encounter with primary health care corporation (PHCC) in Qatar during the period 2017-2022. Data on documented falls, demographic variables, and medical comorbidities were extracted from all PHCCs in Qatar. Descriptive and inferential statistics were used to address the aim of the study. RESULTS: A total of 68,194 older adults had at least one encounter with PHCC. The median age was 65.0 years, 58.9% were males, and 32.6% were Qatari nationality. A higher percentage of falls was found in individuals with hypertension (80%), diabetes (74.2%), and dyslipidemia (48.9%), which were also the most prevalent comorbidities. The prevalence of falls was 6.7% (95% CI 6.6-6.9). Compared to individuals aged 60-69 years, individuals aged 70-79, 80-89, and 90-99 had increased odds of falls by 1.6 (95% CI 1.5, 1.8), 2.5 (95% CI 2.2, 2.8), and 2.6 (95% CI 2.0, 3.3), respectively. Females and individuals of Qatari nationality had increased odds of fall by 1.5 (95% CI 1.4, 1.6) and 1.2 (95% CI 1.1, 1.3), respectively. Orthostatic hypotension, syncope, Parkinson's disease, and hip arthritis showed the strongest associations with falls. CONCLUSIONS: Given the growing population of older adults in the Middle East and North African region, falls is a public health concern. The risk factors identified in this study suggest the need for proactive healthcare strategies tailored to the unique needs of older adult populations.

The association between Dental Fluorosis and COL1A2 gene polymorphism among a Tunisian Population.

Dental fluorosis (DF) is a prevalent developmental defect of tooth enamel caused by exposure to excessive fluoride, with the severity dependent on various factors. This study aimed to investigate the association between DF and a specific genetic polymorphism (rs412777) in the COL1A2 gene among a Tunisian population. A case-control study was conducted from July to November 2022, involving a total of 95 participants including 51 cases and 44 controls. Dental examinations and genetic analysis were performed to assess the relationship between the COL1A2 gene polymorphism and DF.The results of allelic distribution revealed that A allele carriers were significantly protected against (DF) when compared to those with the C allele (C vs. A, p = 0.001; OR = 0.375 (0.207-0.672)). This suggests a strong correlation between the presence of the C allele and the risk of developing DF. Additionally, significant association between the CC genotype of rs412777 and an increased risk of DF was found under both codominant and dominant genetic models (P = 0.002 and P < 0.001 respectively).The findings suggest that genetic predisposition plays a relevant role in the development of DF. Further research is needed to explore the potential use of genetic markers for DF and their implications for public health. This study provides the first insights into the genetic factors associated with DF in the Tunisian population, contributing to our understanding of this prevalent dental condition.

Health burden and attributable economic damage of conflict and terrorism in the Eastern Mediterranean Region.

This study aimed to vividly describe the direct and severe health impacts of conflict in the Eastern Mediterranean Region (EMR) using data from the Global Burden of Disease (GBD). It also sought to quantify the staggering portion of economic damage attributable to the health burden of conflict and terrorism. From 1990 to 2019, the region endured the devastating effects of conflict and terrorism. These circumstances led to 64%, 50%, and 35% of all causes of Disability-Adjusted Life Years (DALYs) in Libya, Syria, and Palestine, respectively, in 2011, 2016, and 2008. These figures represent not just statistics but the profound human cost of these conflicts. The health-related economic burden (HEB) due to conflict was estimated at $4.6 billion in Iraq, $3.7 billion in Afghanistan, and $1.7 billion in Libya in current international dollars. However, due to missing data, the HEB could not be calculated for Yemen and Syria despite significant conflict-related DALYs. In 2019, the HEB to Current Health Expenditure (CHE) ratio, which indicates the proportion of the health-related economic burden compared to health expenditure, was 30% in Afghanistan and 25% in Iraq. This high ratio underscores the significant strain that conflict places on the health systems.

Genetic analysis based on 15 autosomal short tandem repeats (STRs) in the Chaouia population, western center Morocco, and genetic relationships with worldwide populations.

The complex demographic history of human populations in North Africa has resulted in a high degree of genetic heterogeneity across the region. However, little is known about the pattern of these genetic variations in its current populations. The present study provides new data on the genetic background of Chaouia, an Arabic-speaking North African population in the western center of Morocco. A random sample of 150 unrelated healthy individuals from Chaouia was assessed using the AmpFLSTR Identifiler kit. The most polymorphic markers were D21S11 and D18S51, with 23 and 22 alleles, respectively. After Bonferroni's correction, two loci (TH01 and D18S51) deviated from Hardy-Weinberg equilibrium. The phylogeny analysis separated North African populations into northeastern and northwestern groups. The Chaouia population was clustered with northwestern Africans. It was the closest to the Berbers of Azrou. The Chaouia shared close genetic affinities with populations from North Africa, the Middle East, and Europe, particularly Iberians, and to a lesser extent with sub-Saharan populations. The pattern of genetic admixture varied across North African populations without a clear correlation between their geographic (northeastern or northwestern) or linguistic identities (Arab or Berber), however, genetic heterogeneity among Berbers was observed. These findings suggest that the diversity observed in North African populations extends geographical and linguistic boundaries. It is further linked to each population's unique and complex demographic history. Human North African population genetics seems to present an intriguing landscape for future studies in the region and its surrounding populations to trace the origins of the genetic heterogeneity observed in these populations.

Low bone mineral density, a neglected condition in North Africa and Middle East: estimates from the Global Burden of Disease Study, 1990-2019.

Due to the high prevalence of low bone mineral density in North Africa and Middle East region, estimating its attributable burden would help to a better understanding of this neglected condition for policymakers and health researchers. This study presented the number of attributable deaths has doubled from 1990 to 2019. PURPOSE: This study provides the latest estimates of the burden of low bone mineral density (BMD) from 1990 to 2019 in North Africa and Middle East (NAME) region. METHODS: The data were extracted from the global burden of disease (GBD) 2019 study to estimate epidemiological indices such as deaths, disability-adjusted life years (DALYs), and summary exposure value (SEV). SEV is a measure of the exposure of the population to a risk factor that considers the amount of exposure by the level of risk. RESULTS: Our findings showed that in 1990-2019, the number of deaths and DALYs attributable to low BMD had almost doubled in the region and caused 20,371 (95% uncertainty intervals: 14,848-24,374) deaths and 805,959 (630,238-959,581) DALYs in 2019. However, DALYs and death rates showed a decreasing trend after age standardization. Saudi Arabia had the highest, and Lebanon had the lowest age-standardized DALYs rates in 2019, with rates of 434.2 (329.6-534.3) and 90.3 (70.6-112.1) per 100,000, respectively. The highest burden attributable to low BMD was in the 90-94 and over 95 age groups. Also, there was a decreasing trend in age-standardized SEV to low BMD for both sexes. CONCLUSION: Despite the decreasing trend of age-standardized burden indices, considerable amounts of deaths and DALYs were attributable to low BMD, especially in the elderly population, in the region in 2019. As the positive effects of proper interventions will be detectable in the long term, robust strategies and comprehensive stable policies are the ultimate solutions to achieving desired goals.

Frequencies of CYP2D6 genetic polymorphisms in Arab populations.

CYP2D6 is a key drug-metabolizing enzyme implicated in the biotransformation of approximately 25% of currently prescribed drugs. Interindividual and interethnic differences in CYP2D6 enzymatic activity, and hence variability in substrate drug efficacy and safety, are attributed to a highly polymorphic corresponding gene. This study aims at reviewing the frequencies of the most clinically relevant CYP2D6 alleles in the Arabs countries. Articles published before May 2021 that reported CYP2D6 genotype and allelic frequencies in the Arab populations of the Middle East and North Africa (MENA) region were retrieved from PubMed and Google Scholar databases. This review included 15 original articles encompassing 2737 individuals from 11 countries of the 22 members of the League of Arab States. Active CYP2D6 gene duplications reached the highest frequencies of 28.3% and 10.4% in Algeria and Saudi Arabia, respectively, and lowest in Egypt (2.41%) and Palestine (4.9%). Frequencies of the loss-of-function allele CYP2D6*4 ranged from 3.5% in Saudi Arabia to 18.8% in Egypt. The disparity in frequencies of the reduced-function CYP2D6*10 allele was perceptible, with the highest frequency reported in Jordan (14.8%) and the lowest in neighboring Palestine (2%), and in Algeria (0%). The reduced-function allele CYP2D6*41 was more prevalent in the Arabian Peninsula countries; Saudi Arabia (18.4%) and the United Arab Emirates (15.2%), in comparison with the Northern Arab-Levantine Syria (9.7%) and Algeria (8.3%). Our study demonstrates heterogeneity of CYP2D6 alleles among Arab populations. The incongruities of the frequencies of alleles in neighboring countries with similar demographic composition emphasize the necessity for harmonizing criteria of genotype assignment and conducting comprehensive studies on larger MENA Arab populations to determine their CYP2D6 allelic makeup and improve therapeutic outcomes of CYP2D6- metabolized drugs.

The Pandemic of Coronary Heart Disease in the Middle East and North Africa: What Clinicians Need to Know.

PURPOSE OF REVIEW: Coronary heart disease (CHD) is the leading cause of morbidity, mortality, and disability in the Middle East and North Africa (MENA). While the prevention, diagnosis, and management of CHD have been detailed in international guidelines, we aimed in this review to quantify the pandemic of CHD in the MENA region and highlight regional patient characteristics, clinical challenges, and future directions to optimize CHD care in the region. RECENT FINDINGS: Patients with CHD in the MENA feature younger age at presentation and worse prognosis in women. Despite the high burden of CHD risk factors, many of these factors remain underrecognized, undertreated, and uncontrolled. Additionally, CHD care is hampered by poor patient awareness, inefficient preventive strategies, and limited access to guideline-recommended therapeutics. All stakeholders involved in healthcare should work together to develop and execute strategies aimed at tackling the burden of CHD in the MENA.

Correlation between KRAS and NRAS mutational status and clinicopathological features in 414 cases of metastatic colorectal cancer in Morocco: the largest North African case series.

BACKGROUND: Advances in molecular biology have improved understanding of the molecular features of carcinogenesis and progression of colorectal cancer. It is clear that the efficacy of anti-EGFR depends upon the RAS mutational status, since any mutation in RAS is associated with resistance to anti-EGFR therapy. The aim of this study is to report the largest North African description of KRAS and NRAS status in metastatic colorectal cancer and to describe the association of these mutations with clinicopathological characteristics. METHODS: This is a prospective study of all consecutive unselected metastatic colorectal cancer samples, collected from the Laboratory of Pathology at the National Institute of Oncology of Rabat, Morocco, from January 1st 2020 to December 31st 2021. The molecular analysis was performed on the Idylla™ platform (fully automated real-time polymerase chain reaction-based assay) for KRAS and NRAS mutations in exons 2, 3 and 4. These mutations were correlated to gender, primary tumor site, histological type and degree of differentiation of tumor using adequate statistical methods. RESULTS: Four hundred fourteen colorectal tumors were screened for KRAS and NRAS mutations. These mutations occurred in 51.7% of tumors for KRAS (mainly in exon 12) and in 3% of tumors for NRAS. There was a significant correlation between NRAS mutation and age of colorectal patients in this study. The low rate of invalid RAS tests (1.7% for KRAS and 3.1% for NRAS) was certainly obtained due to the strict respect of pre-analytical factors such as cold ischemia time and formalin fixation. CONCLUSION: We report the largest North African analysis of NRAS and KRAS status in colorectal metastatic patients. This study showed the ability in low middle income countries to perform a high rate of valid tests and the unusual trend towards older patients for NRAS mutations.