Association of a CYP4A11 polymorphism and hypertension in the Mongolian and Han populations of China

Abstract

ABSTRACT. Human cytochrome P450 4A11 (CYP4A11) plays a role in the regulation of blood pressure through the conversion of arachidonic acid into 20-hydroxyeicosatetraenoic acid (20-HETE). We therefore investigated the association between a CYP4A11 polymorphism (rs9333025) with hypertension in the Mongolian and Han ethnic groups. We studied 514 Mongolians in a pastoral area, including 201 hypertension patients and 313 normotensive controls, and 524 Han individuals in an urban area, including 215 hypertension patients and 309 normotensive controls. Genotyping was performed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP). Genotype, allele, and dominant inheritance differed significantly between the Mongolian and Han populations (P = 0.006, P = 0.002, and P = 0.003, respectively). Significant differences were also observed in these factors when considering only males (P = 0.001, P = 0.003, and P = 0.001, respectively). For the Han population, recessive inheritance differed significantly between hypertension patients and controls and between male patients and controls (P = 0.005 and P = 0.049, respectively). The genotypic, allelic, and dominant frequencies differed significantly between hypertension patients in both populations (P = 0.019, P = 0.035, and P = 0.024, respectively). The genotypic frequency in Mongolian male patients was significantly different from that in Han male patients (P = 0.009). Higher body mass index, triglycerides, and lower high-density lipoprotein were associated with increased risk of developing hypertension in the Han population. The GG genotype was in higher frequency in the Mongolian population, indicating that it is a high risk factor for hypertension. Mongolian men were at higher risk of developing hypertension.

Cytochrome4A11Genetic Polymorphisms Increase Susceptibility to Ischemic Stroke and Associate with Atherothrombotic Events After Stroke in Chinese

“…We showed that the CYP4A11 rs9333025 variation, but not CYP4A11 rs2269231, CYP4F2 rs2108622, or CYP4F2 rs3093135, was independently associated with IS. These results are consistent with those of previous studies (Fu et al, 2008a(Fu et al, , 2008c(Fu et al, , 2012Liang et al, 2014) and suggest that mutations in CYP4A11 may contribute to altered 20-HETE production, which could ultimately lead to increased risk for stroke.…”

Interaction BetweenCYP4F2rs2108622 andCPY4A11rs9333025 Variants Is Significantly Correlated with Susceptibility to Ischemic Stroke and 20-Hydroxyeicosatetraenoic Acid Level

“…Our results were consistent with those of previous studies (Fu et al, 2008a;Ding et al, 2010;Liang et al, 2014), but contradicted the findings of some other studies (Fava et al, 2008;Fu et al, 2008b;Ward et al, 2008;Deng et al, 2010;Munshi et al, 2012). For instance, Ward et al (2008) reported that a single polymorphism in the CYP4F2 gene, but not the CYP4A11 gene, is associated with increased 20-HETE secretion and BP.…”

20-HETE in the regulation of vascular and cardiac function

“…Also, in humans a deficiency in 20-HETE synthesis and/or action, measured as decreased urinary excretion in response to salt loading, has been linked to salt-sensitive hypertension (Laffer et al, 2008; Laffer, Laniado-Schwartzman, Wang, Nasjletti, & Elijovich, 2003a; Laffer, Laniado-Schwartzman, Wang, Nasjletti, & Elijovich, 2003b). Polymorphisms in the CYP4A11 gene that reduce its catalytic activity by more than 50% are associated with a decrease in the urinary excretion of 20-HETE and the development of salt-sensitive hypertension (Gainer et al, 2005; Gainer et al, 2008; Laffer et al, 2008; Liang et al, 2014; Mayer et al, 2006). …”