rs1800544

This is a upstream gene variant variant in the ADRA2A gene.

Key Literature Trait Associations

Methylphenidate Response in ADHD

ADRA2A rs1800544 (-1291C>G) is a promoter variant upstream of the alpha-2A adrenergic receptor gene. The G allele is associated with significantly greater improvement in ADHD symptom scores during methylphenidate treatment (OR 3.08). The alpha-2A receptor mediates norepinephrine signaling in the prefrontal cortex, and this variant may alter receptor expression, affecting stimulant and alpha-2 agonist (guanfacine, clonidine) drug response.

Allele G
OR 3.08
p 2.0e-4
Meta-analysis

Alpha-2 Adrenergic Agonist Response

ADRA2A -1291C>G is a promoter variant that affects alpha-2A adrenergic receptor expression. The G allele is associated with reduced receptor density and diminished clinical response to alpha-2 agonists including clonidine and methyldopa for hypertension. This variant has also been implicated in variable response to methylphenidate and guanfacine for ADHD treatment.

Tong AW et al. MicroRNA profile analysis of human prostate cancers. Cancer Gene Therapy 16(3):206-216 (2009)
Allele G
OR
p
Candidate gene study

ClinVar annotation

Likely Benign☆☆☆
1 submitter

not specified

View on ClinVar →

Research that mentions this SNP (6)

Genotyping of single nucleotide polymorphisms related to attention-deficit hyperactivity disorder
MethodsN=30Luis A. Tortajada-Genaro et al.(2016)· Analytical and Bioanalytical Chemistry

This paper develops and compares two microarray-based genotyping methods (ASO and ASA) for three ADHD-related SNPs: rs1800544 (ADRA2A), rs5569 (SL6CA2), and rs1799971 (OPRM1). The ASA approach demonstrated superior performance with 100% accuracy, shorter analysis time (3 hours), and lower DNA requirement (4 ng) compared to ASO. Both methods enable rapid, cost-effective pharmacogenetic testing suitable for decentralized clinical laboratories.

Traits studied:Attention-deficit/hyperactivity disorder (ADHD)Drug response to methylphenidate and amphetaminesRisk for substance abuse comorbidity
Polymorphism in alpha 2A adrenergic receptor gene is associated with sialorrhea in schizophrenia patients on clozapine treatment
AssociationN=237Anssi Solismaa et al.(2014)· Human Psychopharmacology: Clinical and Experimental

This dissertation examined pharmacogenetic associations with clozapine adverse effects in 237 Finnish schizophrenia patients. ADRA2A rs1800544 was associated with clozapine-induced sialorrhea (OR 2.13, 95% CI: 1.17-3.88, p=0.013). Eight HNMT SNPs in complete linkage disequilibrium (r²=1) were associated with sedation. CHRM3 rs685548 and weighted genetic risk scores from HTR4, HTR7, TPH1, CHRM2, ABCB1, and OPRM1 were associated with anticholinergic symptoms.

Traits studied:Anticholinergic symptomsClozapine pharmacokineticsClozapine-induced sialorrheaConstipationSchizophrenia (treatment-related adverse effects)Sedation
Association of RANBP1 haplotype with smooth pursuit eye movement abnormality
ReviewHyun Sub Cheong et al.(2011)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

Traits studied:Alzheimer diseaseAntipsychotic drug responseAntipsychotic drug side effectsAnxiety disordersBipolar disorderCNS disordersDepressive disorderParkinson's diseasePsychotic disordersSchizoaffective disorderSchizophreniaTardive dyskinesiaVascular dementia
Influence of NOS1 on Verbal Intelligence and Working Memory in Both Patients With Schizophrenia and Healthy Control Subjects
ReviewGary Donohoe et al.(2009)· Archives of General Psychiatry

This comprehensive review synthesizes genomic and pharmacogenomic research in schizophrenia, discussing over 200 candidate genes associated with psychotic disorders, genetic mechanisms including copy number variants and microRNA alterations, and pharmacogenomic factors affecting antipsychotic efficacy and safety. Key genes covered include dopamine receptors (DRD1-5), dysbindin (DTNBP1), DISC1, neurotrophic factors, and metabolic enzymes such as CYP2D6, CYP3A4, and COMT, with emphasis on genotype-phenotype correlations in antipsychotic response and side effects.

Traits studied:Antipsychotic drug response and efficacyAntipsychotic drug safety and side effectsAttention-deficit hyperactivity disorderAutismBipolar disorderCognitive function in schizophreniaMajor depressive disorderMental retardationObsessive-compulsive disorderParkinson's diseasePsychotic disordersSchizophreniaTardive dyskinesia
Candidate gene studies of ADHD: a meta-analytic review
Meta-analysisIan R. Gizer et al.(2009)· Human Genetics

Meta-analytic review of candidate gene studies for childhood ADHD examining 19 genes. Significant associations identified for DAT1 (3' UTR VNTR: OR=1.12, p=0.028; rs27072: OR=1.20, p=0.006), DRD4 (exon 3 VNTR: OR=1.33, p=0.00007; rs1800955: OR=1.21, p=0.007), DRD5, 5HTT, HTR1B (rs6296: OR=1.11, p=0.010), and SNAP25 (rs3746544: OR=1.15, p=0.030).

Traits studied:Attention-deficit/hyperactivity disorderChildhood ADHD
Support for association between ADHD and two candidate genes: NET1 and DRD1
AssociationN=484Bobb AJ et al.(2005)· American Journal of Medical Genetics Part B: Neuropsychiatric Genetics

This association study examined 20 polymorphisms from 12 candidate genes in 163 ADHD probands and 129 controls, finding significant associations with two genes: NET1 (rs998424 P=0.009, rs3785157 P=0.002) and DRD1 (rs4532 OR=1.63 P=0.006, rs265981 OR=1.61 P=0.008). The study used both family-based transmission disequilibrium tests and case-control analyses. No significant effects were detected on cognitive, behavioral, or brain MRI measurements.

Traits studied:Attention deficit hyperactivity disorder (ADHD)

Gene information from NCBI Gene. Variant classifications from ClinVar.

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