尽管许多不同的基因很有可能对高血压有贡献，科学家发现了一个基因可能控制着收缩压和舒张压。美国约翰霍普金斯医学院的Yen-Pei Chang及其同事扫描了旧规阿米什人（Old Order Amish） 受试者的基因组中的成千上万个遗传标记，从而确定与血压有关的基因。
现代阿米什人群来自一小群祖先，而且拥有相对同质的生活方式，这让发现导致复杂疾病的基因的工作更加容易。在阿米什受试者身上，这组作者发现携带一种调控肾脏盐的运输的蛋白质的遗传变异的人们有更高的收缩压，他们比没有这种变异的人们的收缩压平均高3.3mmHg。把这些结果与其它的对非阿米什人的研究进行比较后，这组作者发现了该基因对血压的类似效应，尽管其效应较小。这组科学家提出，这个称为STK39的基因影响着肾脏细胞的这种蛋白质的浓度，这有助于控制身体的钠排泄。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
