ArticleProceedings of the National Academy of Sciences of the United States of America2009
From the Cover: Whole-genome association study identifies STK39 as a hypertension susceptibility gene.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00896389 (The Relationship Between Serine Threonine Kinase 39), which is not on this map. Cited by 158 papers, 8 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
The Relationship Between Serine Threonine Kinase 39 (STK39) Genotypes, Salt Sensitivity, Thiazide Diuretics-induced Blood Pressure Response
Who cites it
158 citing papers in PubMed, 8 syntheses or guidelines pooled it, 295 citations in OpenAlex.
- A meta-analysis of genome-wide association studies identifies 17 new Parkinson's disease risk loci.Nature genetics · 2017Pooled it
- The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals.Nature genetics · 2016Pooled it
- Selecting instruments for Mendelian randomization in the wake of genome-wide association studies.International journal of epidemiology · 2016Pooled it
- A meta-analytical assessment of STK39 three well-defined polymorphisms in susceptibility to hypertension.Scientific reports · 2016Pooled it
- STK39 polymorphism is associated with essential hypertension: a systematic review and meta-analysis.PloS one · 2013Pooled it
- A statistical method for region-based meta-analysis of genome-wide association studies in genetically diverse populations.European journal of human genetics : EJHG · 2012Pooled it
- Imputation of sequence variants for identification of genetic risks for Parkinson's disease: a meta-analysis of genome-wide association studies.Lancet (London, England) · 2011Pooled it
- Discovery and replication of novel blood pressure genetic loci in the Women's Genome Health Study.Journal of hypertension · 2011Pooled it
- TET2 and CSMD1 genes affect SBP response to hydrochlorothiazide in never-treated essential hypertensives.Journal of hypertension · 2015Trial
- Salt sensitivity of blood pressure is associated with polymorphisms in the sodium-bicarbonate cotransporter.Hypertension (Dallas, Tex. : 1979) · 2012Trial
- Genes involved in vasoconstriction and vasodilation system affect salt-sensitive hypertension.PloS one · 2011Trial
- Lack of association between polymorphisms in STK39, a putative thiazide response gene, and blood pressure response to hydrochlorothiazide.Pharmacogenetics and genomics · 2010Trial
- The kidney distal tubule potassium switch, modern diet and hypertension.Nature reviews. Nephrology · 2026Review
- Association of ATP2B1 and STK39 gene variants with blood pressure levels in patients with essential hypertension.Laboratory medicine · 2026Article
- Electrochemical analysis of miRNA for liquid biopsy.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2026Article
- Partitioned polygenic scores show mechanistic heterogeneity in type 2 diabetes and hypertension comorbidity.Nature communications · 2026Article
- Kinase interaction analysis predicts actions of the WNK-OSR1/SPAK pathway.Communications biology · 2025Article
- STK39-mediated amplification of γ-H2A.X promotes homologous recombination and contributes to PARP inhibitor resistance.Nucleic acids research · 2024Article
- Navigating the multifaceted intricacies of the NaPhysiological reviews · 2024Review
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
98 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
22 authors at 6 institutions in 1 country.
Funding
Abstract
Hypertension places a major burden on individual and public health, but the genetic basis of this complex disorder is poorly understood. We conducted a genome-wide association study of systolic and diastolic blood pressure (SBP and DBP) in Amish subjects and found strong association signals with common variants in a serine/threonine kinase gene, STK39. We confirmed this association in an independent Amish and 4 non-Amish Caucasian samples including the Diabetes Genetics Initiative, Framingham Heart Study, GenNet, and Hutterites (meta-analysis combining all studies: n = 7,125, P < 10(-6)). The higher BP-associated alleles have frequencies > 0.09 and were associated with increases of 3.3/1.3 mm Hg in SBP/DBP, respectively, in the Amish subjects and with smaller but consistent effects across the non-Amish studies. Cell-based functional studies showed that STK39 interacts with WNK kinases and cation-chloride cotransporters, mutations in which cause monogenic forms of BP dysregulation. We demonstrate that in vivo, STK39 is expressed in the distal nephron, where it may interact with these proteins. Although none of the associated SNPs alter protein structure, we identified and experimentally confirmed a highly conserved intronic element with allele-specific in vitro transcription activity as a functional candidate for this association. Thus, variants in STK39 may influence BP by increasing STK39 expression and consequently altering renal Na(+) excretion, thus unifying rare and common BP-regulating alleles in the same physiological pathway.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.