The perception of genetic diseases and premarital screening tests in the central region of Saudi Arabia.

The prevalence of consanguineous marriages (CMs) varies worldwide from one country to another. However, the Middle East stands out as a region with a notably high rate of CMs. CM is particularly widespread in Saudi Arabia, where the prevalence of autosomal recessive genetic diseases has increased. This study aims to identify the Saudi population's awareness of genetic diseases and premarital screening tests (PMSTs). It also seeks to understand couples' perceptions of genetic diseases before and after marriage and their attitudes towards PMSTs and genetic counselling (GC) in reducing the risk of CM. Through the administration of online questionnaires, this cross-sectional study surveyed 2,057 participants to assess their awareness of genetic diseases and their understanding of testing and preventive measures for inherited diseases. Descriptive analysis, nonparametric chi-square tests and logistic regressions were performed to assess the association of categorical responses. This study included 2,035 Saudi Arabian respondents. A significant correlation was found between positive family history and partner selection (p = 0.001), as well as between partnering within the same tribe (p = 0.000139), with a different tribe (p = 0.000138) and from another family (p = 0.000489). About 91.3% of participants expressed agreement regarding the need to enhance public awareness and knowledge concerning genetic disorders, while 87% agreed that increased government regulations are required to prevent the spread of genetic diseases in affected families. Despite increased awareness of genetic diseases and PMSTs, there appears to be a lack of understanding regarding the limitations of PMSTs. The persistently high rate of CM underscores the challenge of altering marriage customs. Further governmental efforts are required to promote awareness of alternative reproductive options, establish new regulations and expand screening programmes.

Molecular Role of Asn680Ser and Asp37Glu Missense Variants in Saudi Women with Female Infertility and Polycystic Ovarian Syndrome.

Female infertility (FI) is a global health issue. Polycystic ovary syndrome (PCOS) is a common cause of FI. The renalase gene (RNLS) is associated with FI and other human diseases. Based on the documented missense variants, rs6166 and rs2296545 single-nucleotide polymorphisms (SNPs) were not identified in Saudi women with FI and PCOS. This study aimed to investigate the molecular role of the two SNPs in Saudi women with FI and PCOS. In this cross-sectional study, 96 healthy controls, 96 women with FI, and 96 women with PCOS were recruited. DNA was isolated, and polymerase chain reactions and Sanger sequencing analysis were performed using rs6166 and rs2296545 SNPs. The data obtained from the three groups were used to perform statistical analyses based on genotype, allele frequencies, regression models, and ANOVA analysis. Both rs6166 and rs2296545 had no role in FI or PCOS in Saudi women. A predicted reason for non-association in Saudi women could be the role of elderly women in the controls compared with women with FI and PCOS. Moreover, age, weight, and body mass index were higher in the control group than the FI and PCOS groups. In conclusion, rs6166 and rs2296545 SNPs were not associated with FI or PCOS in Saudi women.

p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells.

Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source of mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated with such cancer mutations. To better understand the processes directing A3B over-expression in cancer, and possible therapeutic avenues for targeting A3B, we have investigated the regulation of A3B gene expression. Here, we show that A3B expression is inversely related to p53 status in different cancer types and demonstrate that this is due to a direct and pivotal role for p53 in repressing A3B expression. This occurs through the induction of p21 (CDKN1A) and the recruitment of the repressive DREAM complex to the A3B gene promoter, such that loss of p53 through mutation, or human papilloma virus-mediated inhibition, prevents recruitment of the complex, thereby causing elevated A3B expression and cytosine deaminase activity in cancer cells. As p53 is frequently mutated in cancer, our findings provide a mechanism by which p53 loss can promote cancer mutagenesis.

Artificial intelligence in Immuno-genetics.

Rapid advancements in the field of artificial intelligence (AI) have opened up unprecedented opportunities to revolutionize various scientific domains, including immunology and genetics. Therefore, it is of interest to explore the emerging applications of AI in immunology and genetics, with the objective of enhancing our understanding of the dynamic intricacies of the immune system, disease etiology, and genetic variations. Hence, the use of AI methodologies in immunological and genetic datasets, thereby facilitating the development of innovative approaches in the realms of diagnosis, treatment, and personalized medicine is reviewed.

A Comprehensive Two-Decade Analysis of Lymphoma Incidence Patterns in Saudi Arabia.

Background: Lymphomas account for approximately 10% of all cancer cases among the Saudi population. Even when separated, Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) are in the top ten most commonly diagnosed cancers among Saudi men and women. Despite the substantial cost of HL and NHL to public health, the resources to assess their impact are insufficient. This study provides a two-decade detailed assessment of lymphoma incidence trends in the Saudi population. Methods: Analysis of the Saudi Cancer Registry (SCR) data for various incidence metrics from 2001 to 2020 was conducted. Joinpoint regression analysis was further performed to investigate temporal trends globally and by age group, gender, and administrative region. Results: HL cases grew by 174.1%, whereas NHL cases increased by only 80% for that time period. The HL overall Age-Standardized Incidence Rate (ASR) increased by 100% for both genders combined but remained unchanged for NHL. The median age at diagnosis for HL (20-30 years) and NHL (46-57 years) was lower than in many other nations. Our model identified increasing trends for HL with annual percentage changes (APCs) of 2.94% (CI: 2.2-3.7) and 3.67% (CI: 2.6-4.7) for males and females, respectively. The rise was mainly among young groups under 40. On the contrary, the NHL cohort revealed notable declining tendencies. We discovered alarming rates of HL in Saudi Arabia's APC (2.23% for males and 3.88% for females) and ASR compared to other Western countries. Overall, the majority of the patients presented with advanced-stage disease at a younger age and with slight male predominance. Conclusions: The overall incidence of lymphoma (especially HL) has been rising among Saudis. Implementation of secondary and tertiary prevention measures, as well as management of modifiable risk factors, is warranted.

Fusing Peptide Epitopes for Advanced Multiplex Serological Testing for SARS-CoV-2 Antibody Detection.

The tragic COVID-19 pandemic, which has seen a total of 655 million cases worldwide and a death toll of over 6.6 million seems finally tailing off. Even so, new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continue to arise, the severity of which cannot be predicted in advance. This is concerning for the maintenance and stability of public health, since immune evasion and increased transmissibility may arise. Therefore, it is crucial to continue monitoring antibody responses to SARS-CoV-2 in the general population. As a complement to polymerase chain reaction tests, multiplex immunoassays are elegant tools that use individual protein or peptide antigens simultaneously to provide a high level of sensitivity and specificity. To further improve these aspects of SARS-CoV-2 antibody detection, as well as accuracy, we have developed an advanced serological peptide-based multiplex assay using antigen-fused peptide epitopes derived from both the spike and the nucleocapsid proteins. The significance of the epitopes selected for antibody detection has been verified by in silico molecular docking simulations between the peptide epitopes and reported SARS-CoV-2 antibodies. Peptides can be more easily and quickly modified and synthesized than full length proteins and can, therefore, be used in a more cost-effective manner. Three different fusion-epitope peptides (FEPs) were synthesized and tested by enzyme-linked immunosorbent assay (ELISA). A total of 145 blood serum samples were used, compromising 110 COVID-19 serum samples from COVID-19 patients and 35 negative control serum samples taken from COVID-19-free individuals before the outbreak. Interestingly, our data demonstrate that the sensitivity, specificity, and accuracy of the results for the FEP antigens are higher than for single peptide epitopes or mixtures of single peptide epitopes. Our FEP concept can be applied to different multiplex immunoassays testing not only for SARS-CoV-2 but also for various other pathogens. A significantly improved peptide-based serological assay may support the development of commercial point-of-care tests, such as lateral-flow-assays.

A conceptual model of factors associated with health-related quality of life in men and women with knee osteoarthritis in Riyadh, Saudi Arabia: A multicenter cross-sectional study.

This study used a conceptual model to examine the factors influencing physical, mental, and overall health-related quality of life (HRQoL) in women and men aged 45 and older with knee osteoarthritis (KOA) in Saudi Arabia. In this multicenter cross-sectional study, we randomly included 356 individuals aged 45 years or above with doctor-confirmed KOA from the orthopedic and physiotherapy departments of the 5 tertiary hospitals in Riyadh, Saudi Arabia, between March 2016 and March 2017. We split all participants into men (n = 146) and women (n = 210) based on gender. A conceptual model was developed using the HRQoL influential potential factors, such as age, sex, education, occupation, and way of eating (sociodemographic), and clinical factors, such as osteoarthritis knee and its severity, duration, pain, and body mass index. The 36-item short form health survey and its subscales of the physical composite scale and mental composite scale were used to evaluate overall HRQoL, physical, and mental health, respectively. We used unadjusted multiple linear regression analyses to investigate the associations between gender-specific potential factors and HRQoL outcomes. Women and men aged between 60 and 64 years were more strongly associated significantly with less physical composite scale score by -3.17, (standard error [SE] = 1.71, P = .021) and -3.18 (SE = 1.69, P = .023) respectively, followed by the primary school or less education by -3.40 (SE = 1.27, P = .0002), severe KOA of -8.94 (SE = 0.99, P < .001), eating on the floor bending the knee of -3.93 (SE = 1.63, P = .042), and pain of -2.39 (SE = 0.26, P < .0001). Women and men with primary school or less education significantly had low mental composite scale and 36-item short form health survey scores of -3.07 (SE = 1.22, P = .041) and -3.23 (SE = 0.99, P = .018), respectively, followed by severe KOA of -4.07 (SE = 1.22, P = .001) and -6.50 (SE = 0.83, P < .0001) and eating on the floor, extending the knee at -3.35 (SE = 1.74, P = .043). Risk factors like age, education, pain, body mass index, and severe KOA are linked to poor physical, mental, and overall HRQoL among women and men in Saudi Arabia.

Strategy for immunological analysis of pro-inflammatory cytokine marker studies with chronic hepatitis B virus in Southwestern region of Saudi Arabia.

BACKGROUND: Hepatitis B Virus (HBV) is one of the leading causes of infectious disease in the global population, and its prevalence has been increasing globally. Human HBV infection is complex, involving both innate and adaptive immune systems. Cytokines play a role in both physiologic and pathologic processes in the liver. This study was designed to screen serum levels using an enzyme linked immunosorbent assay (ELISA) and genetic variants in the TNF-α and IL6 genes using polymerase chain reactions (PCR). The aim of this study was to screen the serum levels and genotype levels with TNF-α (C-308 T/G-308A) and IL-6 (G-174 C) genes in HBV patients and control subjects. METHODS: In this study, we have selected 50 HBV patients and 40 control subjects from Saudi Population. Patient serum samples was used for measuring the serum levels and PCR analysis using RFLP analysis. Prior to this, HBV patients were confirmed with PCR analysis followed by Sanger sequencing analysis. RESULTS: The current study results confirmed positive association in serum levels (p < 0.05) and negative association with both genotype and allele frequencies in TNF-α (C-308 T) and IL-6 (G-174 C) genes among HBV patients and controls (p > 0.05). Positive associations between blood levels of TNF-α and IL-6 were confirmed, while negative associations were found between PCR investigations involving the TNF-α (G-308A) and IL-6 (G-174 C) genes with the HBV prevalence in the Saudi population. CONCLUSION: This study confirmed serum levels are strongly associated with HBV patients in the Saudi population. However, PCR studies showed the negative association with the couple of variants selected for this study.

Comprehensive Retrospective Analysis of Colorectal Cancer Incidence Patterns in Saudi Arabia.

Colorectal cancer (CRC) is the commonest cancer in Saudi males and the third most common in Saudi females. Although CRC represents a major public health challenge, the resources to evaluate its burden are inadequate. This study aims to elucidate the magnitude of CRC incidence trends in the Saudi population by age, gender, and administrative region. Data for multiple incidence measures were analyzed from the Saudi Cancer Registry (SCR) retrospectively from 2001 to 2018. Temporal trends were further analyzed by age group, gender, administrative region, and globally using joinpoint regression analysis. The number of CRC cases climbed by 335.6% and the disease increased by 56.4% to comprise 12.2% of all cancers cases. The age-standardized incidence rate (ASR) increased by 152% overall, and the median age at diagnosis peaked at 60 and 58 years for males and females, respectively. Riyadh and the Eastern Region had the highest ASR for both genders, peaking at 21.8 and 19.2 for males and 17.4 and 16.5 for females per 100 K population. Our prediction model identified growing trends with annual percentage changes (APCs) of 4.59% in males (CI: 3.1-6.1) and 3.91% among females (CI: 2.4-5.5). Males above 75 years had the highest APC (7.9%, CI: 5.3-10.7), whereas the highest APC among females was found in the age group 70-74 (5.4%, CI: 2.8-8). Globally, APC was the highest for both genders compared to selected countries. CRC incidence is increasing alarmingly in Saudi Arabia and is projected to continue. There is a need for better screening strategies, preventative measures, and awareness-building.

The risk of venous thromboembolism and blood hyperlactatemia is associated with increased mortality among critically ill patients with Covid-19.

INTRODUCTION: Coronavirus disease 2019 (Covid-19) following venous thromboembolism (VTE) and blood hyperlactatemia are associated with higher mortality. However, reliable biomarkers for this association remain to be elucidated. This study investigated the associations of VTE risk and blood hyperlactatemia with mortality among critically ill Covid-19 patients admitted to the intensive care unit (ICU). METHODS: In this single-centre retrospective study, we included 171 patients aged ≥18 years with confirmed Covid-19 admitted to the ICU at a tertiary healthcare clinic in the Eastern region of Saudi Arabia between 1 March 2020 and 31 January 2021. Patients were divided into two groups: survivor and non-survivor. The survivors have been identified as the patients discharged from the ICU alive. The VTE risk was defined using a Padua prediction score (PPS) >4. The blood lactate concentration (BLC) cut-off value >2 mmol/L was used to determine the blood hyperlactatemia. RESULTS: Multi-factor Cox analysis showed that PPS >4 and BLC >2 mmol/L were more likely to be significantly associated with higher odds of ICU mortality in critically ill Covid-19 patients (hazard ratio [HR] = 2.80, 95% confidence interval [CI] = 1.00-8.08, p = 0.050; HR = 3.87, 95% CI = 1.12-13.45, p = 0.033, respectively). The Area under the Curve for VTE and blood hyperlactatemia were 0.62 and 0.85, respectively. CONCLUSION: VTE risk and blood hyperlactatemia have been associated with a higher mortality risk in critically ill Covid-19 patients who are hospitalized in the ICU in Saudi Arabia. According to our findings, these people needed more effective VTE prevention strategies based on a personalized assessment of their risk of bleeding. Moreover, persons without diabetes and other groups with a high risk of dying from COVID-19 may be recognized by measuring glucose as having elevated glucose and lactate jointly.

A study on the immunological vitality of an inflammatory biomarker explored with rs5743708 polymorphism in TLR2 gene among Saudi women confirmed with polycystic ovarian syndrome.

Introduction: Polycystic ovary syndrome (PCOS) is an ovarian health condition as well as a long-term endocrine dysfunction that affects reproductive-aged women. Toll-like receptor 2 (TLR2) gene was linked to PCOS and chronic inflammation, and the prevalence of obesity was rising in Saudi women. Previous studies on rs5743708 polymorphism were documented in the obesity as well as in PCOS women. Aim: In this study, we investigated the molecular role of rs5743708 polymorphism in TLR2 gene among Saudi women diagnosed with PCOS using the Rotterdam criteria. Methods: Blood samples were collected from 220 Saudi women in this hospital-based case-control study; 110 were PCOS women and remaining 110 were non-PCOS (control women). Biochemical analysis was performed on serum samples, and molecular analysis was performed on EDTA blood. Genotyping for rs5743708 polymorphism was performed with polymerase chain reaction-restriction fragment length polymorphism analysis. Results: In both groups, clinical data was calculated using t-test, which revealed both positive (p < 0.05) and negative (p > 0.05) associations. HWE analysis supported the rs5743708 polymorphism (p < 0.05). In the rs5743708 polymorphism, none of the genotypes, genetic models, or allele frequencies were found to be associated with PCOS and non-PCOS women. However, both ANOVA and regression analyses revealed a positive relationship in PCOS with weight and BMI (p < 0.0001). Conclusion: The rs5743708 polymorphism was not associated to PCOS in Saudi women. One of the predictions could be that 42.7% of PCOS and 73.6% of non-PCOS women were obese, and the rs5743708 polymorphism has been linked to both obesity and PCOS in the previous studies. This study suggests screening for additional polymorphisms with a large sample size.

Dissecting the Molecular Role of ADIPOQ SNPs in Saudi Women Diagnosed with Gestational Diabetes Mellitus.

The traditional definition of gestational diabetes mellitus (GDM) is the leading cause of carbohydrate intolerance in hyperglycemia of varying severity, with onset or initial detection during pregnancy. Previous studies have reported a relationship among obesity, adiponectin (ADIPOQ), and diabetes in Saudi Arabia. ADIPOQ is an adipokine that is produced and secreted by adipose tissue involved in the regulation of carbohydrate and fatty acid metabolism. This study investigated the molecular association between rs1501299, rs17846866, and rs2241766 single-nucleotide polymorphisms (SNPs) in ADIPOQ and GDM in Saudi Arabia. Patients with GDM and control patients were selected, and serum and molecular analyses were performed. Statistical analyses were performed on clinical data, Hardy Weinberg Equilibrium, genotype and allele frequencies, multiple logistic regression, ANOVA, haplotype, linkage disequilibrium, as well as MDR and GMDR analyses. The clinical data showed significant differences in various parameters between the GDM and non-GDM groups (p < 0.05). In GDM women with alleles, genotypes, and different genetic models, the rs1501299 and rs2241766 SNPs showed a strong association (p < 0.05). Multiple logistic regression analysis revealed a negative correlation (p > 0.05). This study concluded that rs1501299 and rs2241766 SNPs were strongly associated with GDM in women in Saudi Arabia.

Isolated Congenital Anosmia: Case Report and Literature Review.

Isolated congenital anosmia (ICA) is a rare entity worldwide with poorly understood genetic variation. The diagnosis of ICA is made by exclusion of acquired causes of anosmia. Additionally, magnetic resonance imaging in ICA is essential for diagnosis, as it shows reduced or absent development of olfactory bulbs and shallow olfactory sulci. Here, we present the case of a 21-year-old man who presented to our clinic with complete anosmia since birth. The patient's history was negative for acquired causes of anosmia, and the physical examinations of the ears, nose, throat, head, and neck were all not remarkable. Smell testing revealed complete anosmia. The CT imaging was unremarkable; however, magnetic resonance imaging of the anterior brain and olfactory region showed bilaterally absent olfactory bulbs and olfactory tracts, with a shallow olfactory groove. The patient was then subjected to whole exome sequencing. Bioinformatics analysis was performed on the 37 genes associated with olfactory dysfunction, in which a missense variant was identified in the HS6ST1(NM_004807.3) gene was identified, which insilico tools predicted to be likely pathogenic. The results of this patient's genetic analysis add to the possible genetic culprits reported in ICA cases. Additional genetic analyses are required to validate mutations and understand the heterogeneity of disease representation.

Induction of APOBEC3B expression by chemotherapy drugs is mediated by DNA-PK-directed activation of NF-κB.

The mutagenic APOBEC3B (A3B) cytosine deaminase is frequently over-expressed in cancer and promotes tumour heterogeneity and therapy resistance. Hence, understanding the mechanisms that underlie A3B over-expression is important, especially for developing therapeutic approaches to reducing A3B levels, and consequently limiting cancer mutagenesis. We previously demonstrated that A3B is repressed by p53 and p53 mutation increases A3B expression. Here, we investigate A3B expression upon treatment with chemotherapeutic drugs that activate p53, including 5-fluorouracil, etoposide and cisplatin. Contrary to expectation, these drugs induced A3B expression and concomitant cellular cytosine deaminase activity. A3B induction was p53-independent, as chemotherapy drugs stimulated A3B expression in p53 mutant cells. These drugs commonly activate ATM, ATR and DNA-PKcs. Using specific inhibitors and gene knockdowns, we show that activation of DNA-PKcs and ATM by chemotherapeutic drugs promotes NF-κB activity, with consequent recruitment of NF-κB to the A3B gene promoter to drive A3B expression. Further, we find that A3B knockdown re-sensitises resistant cells to cisplatin, and A3B knockout enhances sensitivity to chemotherapy drugs. Our data highlight a role for A3B in resistance to chemotherapy and indicate that stimulation of A3B expression by activation of DNA repair and NF-κB pathways could promote cancer mutations and expedite chemoresistance.

Author Correction: The responses of cancer cells to PLK1 inhibitors reveal a novel protective role for p53 in maintaining centrosome separation.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

The responses of cancer cells to PLK1 inhibitors reveal a novel protective role for p53 in maintaining centrosome separation.

Polo-like kinase-1 (PLK1) plays a major role in driving mitotic events, including centrosome disjunction and separation, and is frequently over-expressed in human cancers. PLK1 inhibition is a promising therapeutic strategy and works by arresting cells in mitosis due to monopolar spindles. The p53 tumour suppressor protein is a short-lived transcription factor that can inhibit the growth, or stimulate the death, of developing cancer cells. Curiously, although p53 normally acts in an anti-cancer capacity, it can offer significant protection against inhibitors of PLK1, but the events underpinning this effect are not known. Here, we show that functional p53 reduces the sensitivity to PLK1 inhibitors by permitting centrosome separation to occur, allowing cells to traverse mitosis and re-enter cycle with a normal complement of 2N chromosomes. Protection entails the activation of p53 through the DNA damage-response enzymes, ATM and ATR, and requires the phosphorylation of p53 at the key regulatory site, Ser15. These data highlight a previously unrecognised link between p53, PLK1 and centrosome separation that has therapeutic implications for the use of PLK1 inhibitors in the clinic.