A genome-wide gene-based associated study identifies SLC4A4, WWOX and COMMD7 as hypertension susceptibility genes in a Han Chinese population

Abstract

Hypertension [OMIN #145500] is a complex disorder with high prevalence and social impact all over the world, especially in industrialized regions. This study conducts the first genome-wide gene-based association scan for hypertension in a Han Chinese population. By analyzing genome-wide SNP data of 400 matched pairs of young-onset hypertensive patients and normotensive controls genotyped with the Illumina HumanHap550-Duo BeadChip, 100 susceptibility genes of hypertension are identified and then validated by permutation tests. In addition to differential allelic distributions, 17 of the 100 genes also exhibit differentially expressed distributions in case and control groups. These genes provide a good molecular signature for a classification of hypertensive patients and normotensive controls. Among the 17 genes, SLC4A4 encoding the Electrogenic Sodium Bicarbonate Cotransporter 1 Protein and WWOX encoding the WW Domain-Containing Protein are not only identified by our gene-based association scan and gene expression analysis but also replicated by a gene-based analysis of the Hong Kong Hypertension Study. Previous mouse experiments have suggested that SLC4A4 is associated to decreased body weight/size and abnormal ion homeostasis and WWOX is associated to hypoglycemia and hyperphosphatemia. In addition, a novel hypertension gene COMMD7 encoding COMM Domain-Containing Protein 7 is replicated by a gene-based analysis of the WTCCC Hypertension Study. Identification of these genes benefits to enrich a collection of hypertension genes thereby to unravel complex development etiology of hypertension in Han Chinese populations.