Details of primers used for genotyping.

BackgroundIschemic stroke poses a notable global public health challenge, with the Kingdom of Saudi Arabia (KSA) being no exception. This multifaceted condition is affected by a combination of factors, including hypertension, diabetes, and genetic influences. The purpose of the present study was to examine the linkage of long noncoding RNAs (such as ANRIL), plasminogen activator inhibitor-1 (PAI-1), and hepatocyte nuclear factor 1 alpha (HNF1α) gene variations with stroke. Leveraging a substantial cohort comprising both stroke patients and healthy individuals from KSA, our research revealed numerous uncommon genetic variations linked to an increased predisposition to stroke. This insight enhances our comprehension of stroke’s genetic underpinnings and can be invaluable in formulating preventive measures, not only in KSA but also on a global scale.MethodsIn this study we included 100 stroke patients and 100–120 healthy controls from Saudi population. We utilized the amplification refractory mutation system-PCR to genotype the chromosome 9p21 locus, the long noncoding RNA-ANRIL (lncRNA-ANRIL), Hepatocyte Nuclear Factor 1 alpha (HNF1α-A > C [p.I27L]) gene, and the plasminogen activator inhibitor-1 (PAI-1) gene to investigate the association of these gene variations with a stroke. Additionally, WES was performed for 10 stroke patients using the Illumina NovaSeq 6000 platform.ResultsOur investigation revealed significant associations between stroke patients and healthy controls concerning polymorphic variants of lncRNA-ANRIL (A > C), ANRIL (G > A), HNF1α-A > C, and PAI-1-4G > 5G genes (p ConclusionOur findings underscore the significant role of genetic determinants in chromosome 9p21, the lncRNA-ANRIL, HNF1α-A > C (p.I27L), and PAI-1-4G > 5G genes in elevating the risk of stroke. Additionally, we report low, novel, and intermediate-genetic-risk variants in COL4A2, PSEN2, NOTCH3, and RNF2 through WES, emphasizing the need for further investigation in larger cohort studies.