人类和狒狒中SLC34A2变异与钠-锂逆向转运活性的关联

Association of SLC34A2 variation and sodium-lithium countertransport activity in humans and baboons.

作者信息

Zheng Xiaojing, Kammerer Candace M, Cox Laura A, Morrison Alanna, Turner Stephen T, Ferrell Robert E

机构信息

Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.

出版信息

Am J Hypertens. 2009 Mar;22(3):288-93. doi: 10.1038/ajh.2008.355. Epub 2009 Jan 1.

DOI:10.1038/ajh.2008.355

PMID:19119262

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2652891/

Abstract

BACKGROUND

Sodium-lithium countertransport (SLC) activity, an intermediate phenotype of essential hypertension, has been linked to a region of baboon chromosome 5, homologous to human chromosome 4p. Human SLC34A2, located at chromosome 4p15.1-p15.3, is a positional candidate gene for SLC. The specific aim of this study was to identify genetic variants of the SLC34A2 gene in both baboon and human, and to examine the relationship of these polymorphisms with SLC activity and blood pressure.

METHODS

Single-nucleotide polymorphism (SNP) was identified by sequencing the SLC34A2 gene in 24 baboon founders and 94 unrelated individuals. All tag SNPs in SLC34A2 were genotyped in 1,856 individuals from 252 pedigrees of mixed European ancestry. Three SNPs in baboon were genotyped in 634 baboons comprising 11 pedigrees.

RESULTS

In human, one SNP (rs12501856) was found to be significantly associated with SLC individually, though it did not pass multiple testing correction; however, haplotype 2 containing allele C of SNP rs12501856 showed strong evidence of association with SLC (P = 0.0037) after multiple comparison adjustment. This haplotype was also marginally associated with diastolic blood pressure and systolic blood pressure. This finding was confirmed in baboons, where a highly significant association was detected between SLC and baboon SNP Asn136Asn (P = 0.0001). However, the associated SNP did not account for the linkage signal on baboon chromosome 5.

CONCLUSIONS

Consistent results in two different species imply that SLC34A2 is associated with SLC activity and blood pressure.

摘要

背景

钠-锂逆向转运（SLC）活性是原发性高血压的一种中间表型，已与狒狒5号染色体上一个与人4号染色体p同源的区域相关联。位于4号染色体p15.1 - p15.3的人类SLC34A2是SLC的一个位置候选基因。本研究的具体目的是鉴定狒狒和人类中SLC34A2基因的遗传变异，并研究这些多态性与SLC活性和血压的关系。

方法

通过对24只狒狒奠基者和94名无关个体的SLC34A2基因进行测序来鉴定单核苷酸多态性（SNP）。在来自252个欧洲混合血统家系的1856名个体中对SLC34A2中的所有标签SNP进行基因分型。在包含11个家系的634只狒狒中对狒狒中的三个SNP进行基因分型。

结果

在人类中，发现一个SNP（rs12501856）单独与SLC显著相关，尽管它未通过多重检验校正；然而，包含SNP rs12501856等位基因C的单倍型2在多重比较调整后显示出与SLC有很强的关联证据（P = 0.0037）。该单倍型也与舒张压和收缩压有边缘关联。这一发现在狒狒中得到证实，在狒狒中检测到SLC与狒狒SNP Asn136Asn之间有高度显著的关联（P = 0.0001）。然而，相关的SNP并不能解释狒狒5号染色体上的连锁信号。