title: STK39 polymorphisms and blood pressure: an association study in British Caucasians and assessment of cis-acting influences on gene expression.
abstract: BACKGROUND
  Blood pressure (BP) has significant heritability, but the genes responsible remain largely unknown. Single nucleotide polymorphisms (SNPs) at the STK39 locus were recently associated with hypertension by genome-wide association in an Amish population; in vitro data from transient transfection experiments using reporter constructs suggested that altered STK39 expression might mediate the effect. However, other large studies have not implicated STK39 in hypertension. We determined whether reported SNPs influenced STK39 expression in vivo, or were associated with BP in a large British Caucasian cohort.
  
  
  METHODS
  1372 members of 247 Caucasian families ascertained through a hypertensive proband were genotyped for reported risk variants in STK39 (rs6749447, rs3754777, rs35929607) using Sequenom technology. MERLIN software was used for family-based association testing. Cis-acting influences on expression were assessed in vivo using allelic expression ratios in cDNA from peripheral blood cells in 35 South African individuals heterozygous for a transcribed SNP in STK39 (rs1061471) and quantified by mass spectrometry (Sequenom).
  
  
  RESULTS
  No significant association was seen between the SNPs tested and systolic or diastolic BP in clinic or ambulatory measurements (all p > 0.05). The tested SNPs were all associated with allelic expression differences in peripheral blood cells (p < 0.05), with the most significant association for the intronic SNP rs6749447 (P = 9.9 x 10-4). In individuals who were heterozygous for this SNP, on average the G allele showed 13% overexpression compared to the T allele.
  
  
  CONCLUSIONS
  STK39 expression is modified by polymorphisms acting in cis and the typed SNPs are associated with allelic expression of this gene, but there is no evidence for an association with BP in a British Caucasian cohort.
authors.affiliation: Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK. mike.cunnington@ncl.ac.uk
authors.forename: Michael S
authors.initials: MS
authors.lastname: Cunnington
authors.forename: Chris
authors.initials: C
authors.lastname: Kay
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Avery
authors.forename: Bongani M
authors.initials: BM
authors.lastname: Mayosi
authors.forename: Mauro Santibanez
authors.initials: MS
authors.lastname: Koref
authors.forename: Bernard
authors.initials: B
authors.lastname: Keavney
mesh_terms: D000328:Adult; D000483:Alleles; D001794:Blood Pressure / Q000235:genetics*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000235:genetics* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D006113:United Kingdom; D044465:White People / Q000235:genetics
chemical_list: D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human