rs10757278
badMag 4.5This is a intron variant variant in the CDKN2B-AS1 gene.
Key Literature Trait Associations
Myocardial Infarction
rs10757278 is a lead variant at the 9p21.3 locus, the most significant common genetic risk factor for myocardial infarction identified to date. The G allele disrupts a STAT1 binding site within the ANRIL (CDKN2B-AS1) gene, altering expression of the antisense RNA and its downstream targets in vascular tissue. The effect is independent of traditional risk factors (lipids, blood pressure, diabetes) and operates through vascular inflammation and smooth muscle cell proliferation.
Coronary artery disease
rs10757278-G is significantly associated with coronary artery disease (CAD) across multiple ethnicities. A 2019 meta-analysis of 19 studies found the G allele to be a significant CAD biomarker in East Asians, Caucasians, and West Asians. A separate 2019 meta-analysis of 15 studies (Hu et al.) confirmed significant CAD association in Caucasians. The GWAS Catalog records OR=1.28 (95% CI 1.22–1.35; p=1×10⁻²⁰) for this variant in association with CAD-related traits near CDKN2A/CDKN2B. The effect is consistent across populations, with ANRIL dysfunction impairing vascular smooth muscle cell regulation.
Abdominal aortic aneurysm
rs10757278-G is associated with abdominal aortic aneurysm (AAA) across multiple populations. The landmark 2008 Nature Genetics study by Helgadottir et al. (multi-national cohorts) found OR=1.31 (p=1.2×10⁻¹²) for AAA, establishing 9p21.3 as the first locus associated with AAA across populations. This study also identified the same variant associating with intracranial aneurysm (OR=1.29, p=2.5×10⁻⁶), suggesting a shared vascular biology across arterial beds.
Intracranial aneurysm
The G allele of rs10757278 is associated with increased intracranial aneurysm (IA) risk. First identified in the 2008 Helgadottir Nature Genetics study (OR=1.29, p=2.5×10⁻⁶), this association was confirmed in a 2023 meta-analysis (Adamou et al.) which found OR=1.41 (95% CI 1.28–1.56) under the dominant model and OR=1.42 (95% CI 1.29–1.56) under the recessive model. The shared association of rs10757278 with MI, AAA, and IA highlights a common 9p21 vascular risk mechanism.
Ischemic stroke
The G allele of rs10757278 is associated with increased ischemic stroke risk, with the strongest signal in the large-artery atherosclerosis subtype. A 2010 meta-analysis of 8 studies (Anderson et al.) found an overall OR of 1.11 (p=0.001), with notably larger effects in large-artery stroke. A 2022 comprehensive meta-analysis (Bai et al., up to 11,527 cases / 12,216 controls) confirmed rs10757278 among 8 ANRIL SNPs significantly associated with ischemic stroke and especially with large-artery atherosclerosis subtype. A separate 2022 Chinese-population meta-analysis (18,584 individuals) found OR=1.15 (95% CI 1.10–1.20; p<0.0001).
Peripheral artery disease
The 9p21.3 locus, including rs10757278, has been implicated in peripheral artery disease (PAD) given its broad vascular risk architecture, though direct evidence specific to rs10757278 and PAD is more limited than for coronary or cerebrovascular disease. The GWAS Catalog records a beta-based association (beta=0.1268, SE=0.008129; p=3×10⁻⁴²) for the A allele on a vascular phenotype, consistent with the locus influencing peripheral vascular outcomes. Effect is directionally consistent with other vascular associations at this locus.
▶GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (3)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶Research that mentions this SNP (8)
▶Dietary patterns interact with chromosome 9p21 rs1333048 polymorphism on the risk of obesity and cardiovascular risk factors in apparently healthy Tehrani adultsAssociationN=265Mehdi Mollahosseini et al.(2020)· European Journal of Nutrition
This cross-sectional study of 265 healthy Tehrani adults examined interactions between the rs1333048 polymorphism on chromosome 9p21 and dietary patterns on obesity risk. The AA genotype of rs1333048 was associated with increased odds of general obesity (OR 3.11, p=0.048) and central obesity (OR 2.63, p=0.026). Significant gene-diet interactions were observed between legumes dietary pattern and rs1333048 on waist circumference (p=0.047), body fat percentage (p=0.048), BMI (p=0.073), waist-to-height ratio (p=0.063), and C-reactive protein (p=0.042).
▶The 9p21 polymorphism is linked with atrial fibrillation during acute phase of ST-segment elevation myocardial infarctionAssociationN=1,083Marek Kiliszek et al.(2016)· Heart and Vessels
This retrospective analysis of 1,083 STEMI patients from two Polish cardiac registries examined the association between rs10757278 (9p21 locus) and acute arrhythmias. The polymorphic G allele showed a protective effect against atrial fibrillation (AF), with significantly lower minor allele frequency in AF patients (0.40 vs 0.51, p=0.0096). In the recessive model, the GG genotype conferred strong protection [OR 0.41, 95% CI 0.17-0.97, p=0.025 for new-onset AF], independent of age and GRACE score. No association was found between rs10757278 and sustained ventricular tachycardia/fibrillation.
▶A Genetic Variant in the Seed Region of miR-4513 Shows Pleiotropic Effects on Lipid and Glucose Homeostasis, Blood Pressure, and Coronary Artery DiseaseReviewMohsen Ghanbari et al.(2014)· Human Mutation
A comprehensive review of long non-coding RNA (lncRNA) genetic variants identified by GWAS studies in cardiometabolic diseases including coronary artery disease, myocardial infarction, type 2 diabetes, and blood pressure traits. The review highlights key lncRNA loci such as CDKN2B-AS1/ANRIL at 9p21.3 (rs10757278, rs2891168), MIAT (rs4977574, rs10811661), H19 (rs217727), LOC157273 (rs9987289, rs4841132), KCNQ1OT1 (rs231362), and LINC00243 (rs886424), discussing mechanisms of how genetic variants in non-coding RNA regions influence cardiovascular and metabolic disease risk.
▶Common genetic polymorphisms in Moyamoya and atherosclerotic disease in EuropeansAssociationN=108Constantin Roder et al.(2011)· Child's Nervous System
Case-control study of 40 European Moyamoya disease patients versus 68 controls found a significant association between rs599839 (A/G, OR=2.17, 95% CI=1.17-4.05, p=0.01) in the PSRC1 gene and Moyamoya disease, along with three additional SNPs showing borderline significance in ELN and CXCL12 genes. The findings suggest shared genetic pathways between Moyamoya disease and atherosclerotic disease.
▶Type 2 diabetes-associated genetic variants discovered in the recent genome-wide association studies are related to gestational diabetes mellitus in the Korean populationAssociationN=1,501Cho YM et al.(2009)· Diabetologia
This case-control study in 869 Korean women with gestational diabetes mellitus (GDM) and 632 non-diabetic controls examined whether type 2 diabetes-associated genetic variants discovered in recent GWAS are also associated with GDM. Multiple variants showed significant associations with GDM, including rs7756992 and rs7754840 in CDKAL1 (OR 1.55, p=4.17×10⁻⁹), rs10811661 in CDKN2A-CDKN2B (OR 1.49, p=1.05×10⁻⁷), variants in HHEX, rs4402960 in IGF2BP2 (OR 1.18, p=0.03), rs13266634 in SLC30A8 (OR 1.24, p=0.005), and rs7903146 in TCF7L2 (OR 1.58, p=0.038).
▶Sequence variants on chromosome 9p21.3 confer risk for atherosclerotic strokeAssociationN=8,681Andreas Gschwendtner et al.(2009)· Annals of Neurology
This study identified seven SNPs on chromosome 9p21.3 associated with atherosclerotic stroke risk in 4,376 cases and 4,305 controls from Europe and North America. The lead SNP rs1537378 had a pooled odds ratio of 1.21 (95% CI=1.07-1.37, p=0.002) with a population attributable risk of 20.1% for atherosclerotic stroke. The associated variants are located in a region spanning over 100 kb that overlaps genes encoding ANRIL (antisense noncoding RNA), MTAP, CDKN2A, and CDKN2B, implicating this locus in vascular disease pathogenesis.
▶Pharmacogenetics: data, concepts and tools to improve drug discovery and drug treatmentReviewJürgen Brockmöller et al.(2008)· European Journal of Clinical Pharmacology
This comprehensive review article traces the evolution of pharmacogenetics from single-gene analysis to whole-genome approaches. It discusses validated pharmacogenetic biomarkers with clinical impact including CYP2D6, CYP2C9, CYP2C19, TPMT, DPD, VKORC1, UGT1A1, and ADRB1/ADRB2, providing examples of how genetic variants affect drug metabolism and response. The paper emphasizes the importance of integrating pharmacogenetic information into clinical practice and drug development.
▶Interaction Between Poor Glycemic Control and 9p21 Locus on Risk of Coronary Artery Disease in Type 2 DiabetesAssociationN=1,209Doria A. et al.(2008)· JAMA
This case-control and cohort study of 734 type 2 diabetic patients examined the association between the 9p21 locus (tagged by rs2383206) and coronary artery disease (CAD), finding that the risk allele G significantly increased CAD risk (OR=2.37 for homozygotes, p=0.0002). Importantly, the study demonstrated a significant interaction between poor glycemic control and the rs2383206 G/G genotype, with the odds ratio for CAD increasing fourfold (OR=4.27, 95% CI 2.26-8.01) in individuals with both the risk genotype and poor glycemic control, compared to twofold (OR=1.99) without poor glycemic control.
Gene information from NCBI Gene. Variant classifications from ClinVar.
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