rs4291
This is a regulatory region variant variant in the ACE gene.
▶GWAS Catalog Trait Associations (4)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
GWAS Catalog Trait Associations (4)
Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.
▶ClinVar annotation
▶Research that mentions this SNP (4)
▶Polymorphisms in the angiotensin‐converting enzyme gene region predict coping styles in healthy adults and depressed patientsAssociationN=735Angela Heck et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
This study investigated associations between 15 SNPs and one insertion/deletion polymorphism in the ACE gene region with coping styles in 541 healthy adults and 194 depressed patients. The strongest association was rs8066276 (intronic SNP) with the Distraction coping factor (adjusted P=0.009, Cohen's f=0.10) in healthy subjects, where T-allele carriers showed significantly lower Distraction scores. rs4305 showed significant association with Devaluation/Defense coping (adjusted P=0.02, f=0.15). These and other ACE polymorphisms were associated with positive (stress-reducing) coping styles in both samples, suggesting the ACE gene is involved in development of adaptive coping strategies.
▶An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3AssociationN=5,270Todd L. Edwards et al.(2009)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Association analysis of Alzheimer disease candidate genes in 738 families (4704 individuals) and 296 cases/566 controls detected significant haplotype effects in ACE gene (p=0.0004 family, p=0.029 case-control) and putative multilocus associations between ACE, A2M, and LRRTM3 (p<0.001 MDR-PDT). ACE ancestral haplotypes show consistent replication across independent samples with attributable risk explaining ~8-16% of LOAD cases.
▶Confronting complexity in late‐onset Alzheimer disease: application of two‐stage analysis approach addressing heterogeneity and epistasisAssociationN=3,570Tricia A. Thornton‐Wells et al.(2008)· Genetic Epidemiology
This paper presents a two-stage analysis approach to identify genetic heterogeneity and gene-gene interactions in late-onset Alzheimer disease (LOAD). Using Bayesian Classification clustering followed by multifactor dimensionality reduction (MDR), the authors identified LRRTM3 as a primary stratification gene and found that markers in PLAU, ACE, and CDC2 were associated with LOAD specifically within distinct LRRTM3-defined subgroups, suggesting complex gene-gene interactions in LOAD etiology.
▶Common variants of ACE contribute to variable age-at-onset of Alzheimer’s diseaseAssociationN=2,861Patrick G. Kehoe et al.(2004)· Human Genetics
This study examined 2,861 individuals from three European populations to assess the association between ACE gene variants and age-at-onset (AAO) of Alzheimer's disease. Three ACE SNPs (rs4343, rs4291, rs1800764) were genotyped; rs4343 showed strong association with AAO (P<0.0001) with the GG genotype associated with later disease onset, and rs4291 showed independent effects (P=0.0095). The effects were consistent across gender and APOE ε4 carrier status.
About ACE
This gene encodes an enzyme involved in blood pressure regulation and electrolyte balance. It catalyzes the conversion of angiotensin I into a physiologically active peptide angiotensin II. Angiotensin II is a potent vasopressor and aldosterone-stimulating peptide that controls blood pressure and fluid-electrolyte balance. This angiotensin converting enzyme (ACE) also inactivates the vasodilator protein, bradykinin. Accordingly, the encoded enzyme increases blood pressure and is a drug target of ACE inhibitors, which are often prescribed to reduce blood pressure. This enzyme additionally plays a role in fertility through its ability to cleave and release GPI-anchored membrane proteins in spermatozoa. Many studies have associated the presence or absence of a 287 bp Alu repeat element in this gene with the levels of circulating enzyme. This polymorphism, as well as mutations in this gene, have been implicated in a wide variety of diseases including cardiovascular pathophysiologies, psoriasis, renal disease, stroke, and Alzheimer's disease. Regulation of the homologous ACE2 gene may be involved in progression of disease caused by several human coronaviruses, including SARS-CoV and SARS-CoV-2. Alternative splicing results in multiple transcript variants encoding both somatic (sACE) and male-specific testicular (tACE) isoforms. [provided by RefSeq, Sep 2020]
View all ACE variants →Gene information from NCBI Gene. Variant classifications from ClinVar.
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