rs1024323

This is a missense variant in the GRK4 gene.

Key Literature Trait Associations

Antihypertensive Response

GRK4 A142V (rs1024323) is a common missense variant in G protein-coupled receptor kinase 4 that modifies renal dopamine D1 receptor signaling. The 142V variant (T allele) enhances GRK4-mediated phosphorylation and desensitization of D1 receptors, impairing natriuresis and promoting sodium retention. In the PEAR clinical trial, the haplotype containing this variant was associated with reduced atenolol-induced blood pressure lowering.

Vandell AG et al. “G protein receptor kinase 4 polymorphisms: β-blocker pharmacogenetics and treatment-related outcomes in hypertension.” Hypertension (dallas, Tex. : 1979) 60(4):957-964 (2012)

Allele T

OR —

p —

Candidate gene study

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GWAS Catalog Trait Associations (1)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

cigarettes per day measurement

Liu M et al. “Association studies of up to 1.2 million individuals yield new insights into the genetic etiology of tobacco and alcohol use.” Nature Genetics 51(2):237-244 (2019)

Allele T

OR 0.01

p 9.0e-9

N 377,334

Large GWAS

European

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Research that mentions this SNP (1)

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Identification of aDMBT1polymorphism associated with increased breast cancer risk and decreased promoter activity

FunctionalTchatchou S. et al.(2010)· Human Mutation

This functional study identified 60 candidate differential allele-specific expression (DASE) loci in normal breast mammary epithelial cells using genome-wide SNP array analysis and validated them through Sanger sequencing. Key findings include identification of DMBT1 rs2981745 as a causal variant for DASE (DASE=2.03, P=0.0017, FDR=0.014), along with cancer-related genes ZNF331 and USP6 in a breast cancer-relevant pathway network. The study demonstrates that global DASE analysis is a novel approach for identifying breast cancer risk alleles.