A Haplotype of the Catalase Gene Confers an Increased Risk of Essential Hypertension in Chinese Han

Our previous study in an isolated population showed an association between a genetic variant in the catalase gene (CAT) and essential hypertension (EH). This study indicates that three variants in the promoter and 5'-UTR region of CAT are predominant in Chinese Han, and they form two major haplotypes. A case-control study showed that the CATH2 haplotype confers susceptibility to EH (Pgenotype = 0.0017, and Pallilc = 0.00078). Subjects bearing CATH1/CATH2 and CATH2/CATH2 genotypes demonstrated a higher susceptibility to EH than CATH1/CATH1 homozygotes, with odds ratios of 1.474 and 1.625, respectively. Also, CATH1/CATH1 individuals had a later-onset age (P = 0.015). Expression analysis using luciferase reporter vectors indicated that the CATH1 haplotype showed a lower transcriptional activity than the haplotype CATH2 (P < 0.05 in all four cell lines), and we observed similar results in the endogenous allelic expression ratios of CATH1/CATH2 in cell lines. In contrast, most CATH1 haplotypes showed a higher transcription level than CATH2 haplotypes (10 out of I I or 90.9%) in blood from normal individuals (P < 0.01). We therefore hypothesize that CATH1 and CATH2 may play alternating roles at different level of oxidative stress. Hum Mutat 31:272-278, 2010. (C) 2009 Wiley-Liss, Inc.