Xinjiang Kazakh Isolated Group Of Hypertension Associated With Four Genes

Essential hypertension (EH) is a complex disorder influenced by multiple genetic and environmental factors. The genetic basis of essential hypertension is complex. One likely pathway for blood pressure regulation is the renin-angiotensinogen system, which influences both salt and water homeostasis and local blood vessel characteristics. The angiotensinogen (AGT) gene locus of renin-angiotensinogen system has been linked to hypertension in affected relative-pair studies, but the role of the polymorphism at position M235T and A₍-6G remains controversial. Another promising candidate gene is a-Adducin (ADD1), which codes for the cytoskeleton protein a-Adducin. This protein is found in renal tubules and is thought to regulate ion transport through changes in the actin cytoskeleton. A polymorphism, Gly460Trp, found in ADD1 was shown to be associated with hypertension in some populations but controversial in others.The Xinjiang Barkol Kazakh in northwest China are a genetic isolate characterized by ethnically homogeneous and a communal pastoral lifestyle. The incident rate of hypertension in Kazakh is one of the five highest in the 56 nationality of China. The genetic homogeneity and geography stability of the population, along with shared exposure to common environmental variables, provided an excellent opportunity for the study of genetic influence on hypertension. As far as we know, the genetic role contribute to hypertension in Kazakh have not seen reported until now.Objective:To investigate relationship between A₍-6G and M235T polymorphisms in the AGT gene and Gly460Trp of ADD1 gene and essential hypertension in a Xinjiang Kazakh isolate._<sub><sub><sub>Methods:A case-control study was performed in 201 hypertensive and 151 normaltensive (NT) subjects, which were randomly selected from Barkol Kazakh. A previous diabetes and hypertension medical history, body mass index (BMI) were recorded. Plasma glucose, Triglyceride, and Cholesterol were measured. Genome DNA was extracted from white blood cells. The variants A.gG and M235T of AGT gene and Gly460Trp of a-adducin gene were determined using a mutagenically separated polymerase chain reaction technique.Results:No significance deviation from Hardy-Weinberg equilibrium for the A.eG and M235T polymorphisms in the AGT gene and Gly460Trp of ADD1 gene was observed.The distributions of genotypes for A_-6G and Gly460Trp polymorphisms in Xinjiang Kazakh isolate were 47.1%, 18.5%, 34.4%, 25.2%, 57.6%, 17.2%, respectively. The distributions of alleles for A₍-6G and Gly460Trp polymorphisms were 42.1%, 57.9%, 54%, 46%, respectively. The distributions of genotypes and alleles for A₍-6G and Gly460Trp polymorphisms did not differ significantly between the case and control populations.The distributions of genotypes and alleles in Xinjiang Kazakh isolate for AGT M235T MT, TT, MM, T, M were 33.1%, 57%, 9.9%, 73.5%, 26.5%, respectively. The distributions of genotypes of AGT M235T polymorphisms did not differ significantly between EH and NT group, but allele T was more frequent in EH group (80.6%) than in NT group(73.5%, x 2=4.98, p=0.026).Further analyses showed no association between M235T, A₍-6G and Gly460Trp genotypes and BMI, Glu, Triglyceride, cholesterol SBP and DBPConclusion:The T235 allele of the AGT gene confers an increased risk for EH in the Kazakh isolate of northwest china.No evidence was found to suggest an association of the AGT A.eG and ADD1 Gly460Trp polymorphism with essential hypertension in this case-control study.