盡管許多不同的基因很有可能對(duì)高血壓有貢獻(xiàn),，科學(xué)家發(fā)現(xiàn)了一個(gè)基因可能控制著收縮壓和舒張壓。美國(guó)約翰霍普金斯醫(yī)學(xué)院的Yen-Pei Chang及其同事掃描了舊規(guī)阿米什人（Old Order Amish） 受試者的基因組中的成千上萬(wàn)個(gè)遺傳標(biāo)記,，從而確定與血壓有關(guān)的基因。
現(xiàn)代阿米什人群來(lái)自一小群祖先,，而且擁有相對(duì)同質(zhì)的生活方式,，這讓發(fā)現(xiàn)導(dǎo)致復(fù)雜疾病的基因的工作更加容易。在阿米什受試者身上,，這組作者發(fā)現(xiàn)攜帶一種調(diào)控腎臟鹽的運(yùn)輸?shù)牡鞍踪|(zhì)的遺傳變異的人們有更高的收縮壓,，他們比沒(méi)有這種變異的人們的收縮壓平均高3.3mmHg。把這些結(jié)果與其它的對(duì)非阿米什人的研究進(jìn)行比較后,，這組作者發(fā)現(xiàn)了該基因?qū)ρ獕旱念愃菩?yīng),，盡管其效應(yīng)較小。這組科學(xué)家提出,，這個(gè)稱為STK39的基因影響著腎臟細(xì)胞的這種蛋白質(zhì)的濃度,，這有助于控制身體的鈉排泄。（生物谷Bioon.com）
生物谷推薦原始出處：
PNAS December 29, 2008, doi: 10.1073/pnas.0808358106
Whole-genome association study identifies STK39 as a hypertension susceptibility gene
Ying Wanga, Jeffrey R. O'Connella, Patrick F. McArdlea, James B. Wadeb, Sarah E. Dorffa, Sanjiv J. Shahc, Xiaolian Shia, Lin Pand, Evadnie Rampersauda, Haiqing Shena, James D. Kime, Arohan R. Subramanyab, Nanette I. Steinlea, Afshin Parsaf, Carole C. Oberd, Paul A. Wellingb, Aravinda Chakravartig, Alan B. Wederh, Richard S. Cooperi, Braxton D. Mitchella, Alan R. Shuldinera, and Yen-Pei C. Changa,1
aDivision of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201;
bDepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201;
cSection of Cardiology, Department of Medicine, University of Chicago, Chicago, IL 60611;
dDepartment of Human Genetics, University of Chicago, Chicago, IL 60637;
eGeorgetown University School of Medicine, Washington, DC 20057;
fDivision of Nephrology, University of Maryland School of Medicine, Baltimore, MD 21201;
gMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205;
hDepartment of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, MI 48106; and
iDepartment of Preventive Medicine and Epidemiology, Loyola Stritch School of Medicine, Maywood, IL 60153
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.
