Lack of association between polymorphisms in STK39, a putative thiazide response gene, and blood pressure response to hydrochlorothiazide.
STK39 was earlier implicated as a hypertension susceptibility gene and is thought to be involved in the control of Na-Cl co-transporter activity. STK39 has been implicated as a putative thiazide diuretic response gene, as Na-Cl co-transporter activity is inhibited by thiazides. Thus, we aimed to determine whether STK39 is a thiazide response gene. One hundred and ninety-five 'good' and 194 'poor' responders to hydrochlorothiazide (HCTZ) were genotyped for approximately 100 single nucleotide polymorphisms (SNPs) within 5000 bases of STK39. SNPs meeting criteria for advancement to replication analysis (P<0.01), along with those earlier associated with hypertension, were then analyzed in a second population of 201 HCTZ-treated hypertensives. Two SNPs passed screening and were further analyzed. However, neither these, nor earlier implicated SNPs met criteria for significant association with blood pressure response to HCTZ. These data suggest that common variants in STK39 likely do not have a clinically relevant role in blood pressure response to HCTZ in hypertensives.
Duarte
Julio D
JD
Department of Pharmacotherapy and Translational Research and Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, Florida 32610, USA.
Lobmeyer
Maximilian T
MT
Wang
Zhiying
Z
Chapman
Arlene B
AB
Gums
John G
JG
Langaee
Taimour Y
TY
Boerwinkle
Eric
E
Turner
Stephen T
ST
Johnson
Julie A
JA
D000293:Adolescent; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects*; D006801:Humans; D006852:Hydrochlorothiazide / Q000494:pharmacology*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D055815:Young Adult
D006852:Hydrochlorothiazide; D017346:Protein Serine-Threonine Kinases; C486409:STK39 protein, human