Association between SLC20A1 and sodium-lithium countertransport.
Association between SLC20A1 and sodium-lithium countertransport.
复制标题
SLC20A1 与钠-锂逆向转运之间的关联。
DOI：
10.1038/ajh.2011.130
复制
发表时间：
2011
影响因子：
3.2
通讯作者：
Ferrell,RobertE
中科院分区：
文献类型：
--
作者：
Zheng,Xiaojing;Morrison,AlannaC;Turner,StephenT;Ferrell,RobertE
背景钠锂逆转运（SLC）是原发性高血压的发病前标志物。来自人类连锁分析和动力学研究的证据表明，SLC20A1 变异可能会影响红细胞和白细胞中测量的 SLC 活性。SLC20A1 编码钠依赖性磷酸盐协同转运蛋白，并在哺乳动物质膜上广泛表达。在本研究中，我们研究了SLC20A1与SLC活性之间的关系。方法通过基因表达谱分析，我们研究了SLC20A1在高SLC活性个体和低SLC活性个体中的表达情况。为了研究 SLC20A1 与 SLC 的等位基因关联，我们对罗彻斯特家族心脏研究 (RFHS) 受试者中 SLC20A1 的 6 个标签单核苷酸多态性 (tSNP) 进行了基因分型，该研究涉及来自 252 个欧洲混血谱系的 1,815 名个体。通过序列寡基因连锁分析程序(SOLAR)评估SLC20A1与SLC的遗传关联。结果SLC20A1在高SLC活性个体中的表达水平高于在SLC活性低的个体中的表达水平。调整年龄、性别、体重指数、甘油三酯和抗高血压药物治疗后，SLC20A1 中的 4 个 SNP 与 SLC 活性相关（P≤0.05）。最有力的关联证据是 rs4849091 (P= 0.001)，并且即使在多次测试校正后，这种关联仍然显着。结论SLC20A1 中的等位基因变异与 SLC 活性水平相关，从而支持 SLC20A1 参与确定 SLC 活性的假设。美国高血压杂志提前在线出版，2011 年 7 月 28 日； doi：10.1038/ajh.2011.130
BackgroundSodium-lithium countertransport (SLC) is a premorbidity marker of essential hypertension. Evidence from linkage analysis and kinetic studies in humans have suggested thatSLC20A1variations may affect SLC activity as measured in erythrocytes and leukocytes.SLC20A1encodes a sodium-dependent phosphate cotransporter, and is widely expressed on the mammalian plasma membrane. In this study, we investigated the relationship betweenSLC20A1and SLC activity.MethodsBy means of gene expression profiling, we studied the expressions ofSLC20A1in individuals with high SLC activity as compared to those with low SLC activity. In order to investigate the allelic association ofSLC20A1with SLC, we genotyped six tag single-nucleotide polymorphisms (tSNPs) in SLC20A1 in subjects from the Rochester Family Heart Study (RFHS) involving 1,815 individuals from 252 pedigrees of mixed European ancestry. The genetic association ofSLC20A1with SLC was assessed by Sequential Oligogenic Linkage Analysis Routines (SOLAR).ResultsExpression levels of SLC20A1 were higher in individuals with high SLC activity than in those with low SLC activity. Four SNPs inSLC20A1were associated with SLC activity after adjusting for age, sex, body mass index, triglycerides, and antihypertensive drug treatment (P≤ 0.05). The strongest evidence of association was in respect of rs4849091 (P= 0.001), and this association remained significant even after correction for multiple tests.ConclusionsAllelic variations inSLC20A1were associated with the levels of SLC activity, thereby supporting the hypothesis thatSLC20A1is involved in determining SLC activity.American Journal of Hypertensionadvance online publication 28 July 2011; doi:10.1038/ajh.2011.130