Both α- and β-thalassemia (α- and β-thal) are highly prevalent in the population of the Al-Qatif and Al-Ahsa regions in the Eastern Province of Saudi Arabia. This study provides a more precise picture of the α-thal mutations prevalent in 104 transfusion-dependent β-thal patients in the Eastern Province. Detection of α-thal mutations was carried out using the α-globin StripAssay kit. A total of 12 α-thal mutations (21 genotypes) were identified in 33.7% of the chromosomes (46 patients). The heterozygous and homozygous –α^3.7 (α⁺) deletion mutations were the most prevalent in the β-thal patients (21.7%). We identified three α⁰ deletions [– –^MED, – –^FIL and –(α)20.5] that have not been previously reported for the population of Saudi Arabia. The seven point mutations identified in the β-thal patients were: codon 14 [TGG>TAG (α1)], codon 59 [GGC>GAC (α1)] (Hb Adana), polyadenylation signal site (polyA1) [AATAAA>AATAAG (α2)], codon 142 [TAA>TCA (α2)] (Hb Koya Dora), codon 59 [GGC>GAC (α2)] (Hb Adana), initiation codon [ATG>ACG (α2)] and the ααα^{anti 3.7} gene triplication. The Hb Koya Dora mutation occurred at the highest frequency (15.38%). Comparison of the clinical phenotype of β-thal patients, with and without an α-thal mutation, showed that patients with β-thal alone had a significantly elevated level of alanine transaminase (ALT) (mean 72.5 IU/L) and aspartate transaminase (AST) (mean 71.8 IU/L) (p <0.005). In addition, the β-thal patients without an α-thal mutation had a higher percentage of osteoporosis (16.6%), fractures (12.5%), and splenectomies (58.3%). This confirms previous data that the co-inheritance of α-thal in β-thal patients results in the amelioration of the clinical phenotype of β-thal patients. Moreover, the high frequency of α- and β-thal in the Eastern Province of Saudi Arabia and their coinheritance, necessitates the inclusion of α-thal testing in the current pre marital testing program to highlight the risk to the offspring of affected individuals.

Introduction: Detection of β-thalassemia trait or carriers (β-TT) depends significantly on an increase in Hemoglobin A₂ (HbA₂) levels, which is found at low levels (<3%) in normal healthy individuals and elevated levels (≥3.5%) in β-TT individuals. The study was designed to evaluate the reliability of the diagnostic parameter HbA₂ in the differentiation of β-TT and non-β-TT in Saudis. Methods: The widely used high performance liquid chromatography (Variant II Bio-Rad) was used to measure HbA₂ levels in blood. Sanger sequencing was used to screen the variation in globin genes (HBB, HBD, HBA1, and HBA2). All the study subjects were divided into βTT and non-βTT (wild) categories based on the presence or absence of HBB variations and further sub-divided into false positive, true positive, false negative, and true negative, based on HbA₂ values. Results: Out of 288 samples, 96 had HBB gene mutations. Of the 96 β-TT samples, sickle cell trait (SCT) samples (n = 58) were excluded, while the remaining (38 β-TT) were included in the detailed analysis: seven subjects with the HBB mutation had normal HbA₂ (4%). Based on HbA₂ analysis alone, both these groups would be incorrectly diagnosed as normal. Similarly, of the 189 non-β-TT samples, 179 had normal HbA₂, eight had borderline HbA₂, and two had a HbA₂ level above 4%. Based on HbA₂ analysis alone, borderline and >4% HbA₂ individuals, negative for β-TT, can be incorrectly diagnosed as carriers. Conclusion: Given the percentage of samples falling in the HbA₂ “borderline” and “normal” categories, it can be concluded that HbA₂ has a measure of unreliability in the diagnosis of β-thalassemia carriers.

Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Many genetic and environmental risk factors including atherogenic dyslipidemia contribute towards the development of CAD. Functionally relevant mutations in the dyslipidemia-related genes and enzymes involved in the reverse cholesterol transport system are associated with CAD and contribute to increased susceptibility of myocardial infarction (MI). Blood samples from 990 angiographically confirmed Saudi CAD patients with at least one event of myocardial infarction were collected between 2012 and 2014. A total of 618 Saudi controls with no history or family history of CAD participated in the study. Four polymorphisms, rs2230806, rs2066715 (ABCA1), rs5882, and rs708272 (CETP), were genotyped using TaqMan Assay. CETP rs5882 (OR = 1.45, P < 0.005) and ABCA1 rs2230806 (OR = 1.42, P = 0.017) polymorphisms were associated with increased risk of CAD. However, rs708272 polymorphism showed protective effect (B1 vs. B2: OR = 0.80, P = 0.003 and B2B2 vs. B1B1: OR = 0.68, P = 0.012) while the ABCA1 variant rs2066715 was not associated. This study is the first to report the association of these polymorphisms with CAD in the population of the Eastern Province of Saudi Arabia. The rs5882 polymorphism (CETP) showed a significant association and therefore could be a promising marker for CAD risk estimation while the rs708272 polymorphism had a protective effect from CAD.

Circular RNAs (circRNAs) have emerged as crucial cardiovascular regulators through gene expression modulation, microRNA sponging, and protein interactions. Their covalently closed structure confers exceptional stability, making them detectable in blood and tissues as potential biomarkers. This review explores current research examining circRNAs across cardiovascular diseases, including atherosclerosis, myocardial infarction, and heart failure. We highlight the control that circRNA exerts over endothelial function, smooth muscle switching, inflammatory recruitment, and cardiomyocyte survival. Key findings distinguish frequently disease-promoting circRNAs (circANRIL, circHIPK3) from context-dependent regulators (circFOXO3). Compartment-specific controllers include endothelial stabilizers (circGNAQ), smooth muscle modulators (circLRP6, circROBO2), and macrophage regulators (circZNF609), functioning as tunable rheostats across vascular compartments. Overall, the literature suggests that circRNAs represent promising tools in two translational avenues: (i) blood-based multimarker panels for precision diagnosis and (ii) targeted modulation of pathogenic circuits. Clinical translation will require precise cell-type targeting, efficient delivery to cardiovascular tissues, and rigorous mitigation of off-target effects.

The regions of Al-Qatif and Al-Ahssa in the Eastern Province of Saudi Arabia are known for their high prevalence of hemoglobinopathies, including -thalassemia and sickle cell anemia. Previously, the -gene deletion has been demonstrated as highly prevalent among populations residing in these two regions. The present study was conducted in order to investigate the implications of the -globin gene deletion on fetal hemoglobin (HbF) and hemoglobin (2) (HbA(2)) concentrations in patients with transfusion-dependent -thalassemia. A total of 166 Saudi patients with transfusion-dependent -thalassemia and 337 healthy Saudi patients were included in the study. The -(3.7), -(4.2), --(FIL), --(SEA), --(MED) and --((20.5)) gene deletions were identified using multiplex -globin deletion polymerase chain reaction. The present study revealed that the -(3.7) gene deletion is the most prevalent (43.5%) in the Saudi populations that were analyzed and is characterized by the deletion of 3,804 base pairs. Numerous genotypes, namely (-3.7)(2)/(12), (-3.7)(2)/(112), (-3.7)(2)/(-3.7)(2), (-3.7)2(HphI)/(HphI)(12), (-3.7)(2)/(-4.2)(1), (-3.7)(2)/(polyA-1)(1)(2), (-3.7)(12)/(112), (--FIL)/(-3.7)(2) and (-3.7)(2)/(-3.7)(Hb Villiers le Bel)(2) were also identified in the investigated population. Furthermore, a gradual increase in the concentration of HbF and HbA(2) in patients with -thalassemia and the number of -gene deletions was demonstrated; whereas in healthy patients the level of HbA(2) was demonstrated to decrease as the number of -gene deletions increased. Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with -thalassemia rather than -globin deletions. Furthermore, the results of the present study also revealed novel -gene deletion genotypes prevalent in the population studied, namely (12)/(HphI)(12), (HphI)(12)/(HphI)(12), (12)/(Hb Handsworth)(12), -(3.7)(HphI)(2)/(HphI)(12), -(3.7)(2)/-(3.7)(Hb Villiers le Bel)(2) and --(MED)/(HphI)(12).

Breast cancer is one of the major causes of female morbidity and mortality, accounting for ~25% of the total cancer cases in women. Phosphatidylinositol‑4,5‑bisphosphate 3‑kinase catalytic α subunit (PIK3CA) mutations serve a major role in downstream signaling of receptor tyrosine kinases. The present study aimed to elucidate the frequency of exon 9 and 20 mutations of PIK3CA and their role in disease progression. A total of 118 tumor samples from confirmed breast cancer patients were collected from the histopathology laboratory at King Fahd Hospital of the University (Al‑Khobar, Saudi Arabia). Sanger sequencing was performed on extracted DNA to identify the mutations on exons 9 and 20 of PIK3CA. The results were further validated by competitive allele‑specific TaqMan polymerase chain reaction. Three mutations, namely E542K and E545K within exon 9, and H1047R within exon 20, were observed in 25 patients (21.2%). Among these, 18 patients carried the H1047R mutation of the kinase domain, while the remaining 7 patients carried mutations in the helical domain. PIK3CA mutations were associated with the estrogen receptor‑positive/progesterone receptor‑positive (ER+/PR+) group of tumors in contrast to the ER‑/PR‑ group (P=0.021). Furthermore, it was observed that the PIK3CA mutation was associated with a poor disease prognosis. Taken together, the current study emphasized the potential of PIK3CA mutations as an important biomarker for breast cancer classification and the possible use of PIK3CA inhibitor as targeted therapy for breast cancer.