Institute of Human Genetics, Newcastle University, Central Parkway, Newcastle upon Tyne, NE1 3BZ, UK.
BMC Med Genet. 2009 Dec 14;10:135. doi: 10.1186/1471-2350-10-135.
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.
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).
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.
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.
血压（BP）具有显著的遗传性，但负责的基因仍知之甚少。在一项阿什人人群的全基因组关联研究中，STK39 基因座的单核苷酸多态性（SNP）最近与高血压有关；使用报告基因构建体进行瞬时转染实验的体外数据表明，STK39 表达的改变可能介导这种影响。然而，其他大型研究并未将 STK39 牵连到高血压中。我们确定报告的 SNP 是否会影响体内的 STK39 表达，或者是否与英国白种人队列中的血压有关。
通过高血压先证者确定了 247 个白种人家系的 1372 名成员，使用 Sequenom 技术对 STK39 中的报告风险变体（rs6749447、rs3754777、rs35929607）进行基因分型。使用 MERLIN 软件进行基于家庭的关联测试。使用来自 STK39（rs1061471）转录 SNP 杂合的 35 名南非个体外周血细胞 cDNA 中的等位基因表达比，在体内评估顺式作用对表达的影响，并通过质谱（Sequenom）进行定量。
在所测试的 SNP 与诊所或动态测量的收缩压或舒张压之间均未见显著相关性（均 p > 0.05）。测试的 SNP 均与外周血细胞中的等位基因表达差异相关（p < 0.05），其中最显著的关联是内含子 SNP rs6749447（P = 9.9 x 10-4）。在该 SNP 为杂合子的个体中，G 等位基因的平均表达量比 T 等位基因高 13%。
STK39 表达受顺式作用的多态性修饰，所测试的 SNP 与该基因的等位基因表达相关，但在英国白种人队列中没有证据表明与血压有关。
