Correlation Between ACE, CYPllB2 And HSP70 Genes And Hypertension, Atherosclerosis Of "Desert Men"

Background:Taklimakan Desert, the largest desert in China and the second largest in the world, is called "Dead sea". The mean of annual rainfall is 14 mm with the evaporation of 3000 mm. In summer, the sun is incredibly fierce with the temperature of 50-60?. The Keriyans have been found living a nomadic life in the center of the Taklamakan desert, one of the most harsh, hot, arid areas in the world, by Sand-Controlgroup and Oilgravitygroup from Chinese Academy of Sciences in 1958. The "Desert people" Keriyans live in the hot, arid areas of Taklimakan Desert and maintain normal biological functions of the body, have a low incidence of cardiovascular disease. However, little is known about the adaptive compensation in the organism. Essential Hypertension (EH) is the major cardiovascular disease. It has been found that hypertension is a polygenic disease. With the development of molecular biology, the hypertension-relatedgenes has become a hot topic. The rennin-angiotensin system (RAAS) is an important component of blood pressure regulation, playing roles in salt-water homeostasis and vascular tone, and has been suspected to be involved in hypertension. Therefore,genes coding for components of this system are attractive candidates for the investigation of thegenetic basic of EH. Atherosclerotic disease has become the main cause of death in the world and China. Atherosclerosis is the serious ischemic disease. Because of the lack of a effective treatment approach, there are urgent needs for the prevention and treatment of atherosclerosis. Recent studies have found that inflammation plays a crucial role in the pathogenesis of atherosclerosis. However, many studies have found that HSP70gene Polymorphisms may have relationship with atherosclerosis. Objects:In the present study, we explored the physiological characteristics, diet and water quality of "Desert people" in Taklimakan Desert and its association with low prevalence of hypertension. The relationship betweengenetic polymorphisms of ACEgene insertion/deletion (I/D) and aldosterone synthasegene CYP11B2 (C-344T and K173R) with the EH of "Desert Men" in the Taklimakan Desert have been explored. The relationship betweengenetic polymorphisms of HSP70 including HSP70-1 (+190G/C), HSP70-2 (+1267A/G) and HSP70-hom (+2437T/C) with the atherosclerosis of "Desert Men" in the Taklimakan Desert. Methods:We performed an epidemiological survey focusing on diet, water quality and plasma biochemical assays in a randomly selected natural population including 503 individuals known as "desert men" and 273 randomly selected vigor controls in Yutian country of Hetian city. Comparison of twogroups physical condition, static ECG and biochemical index were made. ACE (I/D), CYP11B2 (C-344T, K173R) and HSP70genes (HSP70-1, HSP70-2 and HSP70-hom)genotype were detected by Polymerase chain reaction/restriction fragment length polymorphism (PCR. RFLP) and direct sequencing. The difference betweengenotypegroups were compared for haplotype analysis. A case-control study of the 503 "desert people" who were divided into hypertensiongroup (EH) 50 and normal blood pressure controlgroup (NT) 453 people, using PCR. RFLP and direct sequencing to detect ACE and CYP11B2 (C-344T, K173R)genotype and perform haplotype analysis. Results:The height in male and female "Desert people" was significantly taller than in controls (P<0.001). Both the waist and the body mass index were smaller in "Desert tpeople" than in controls with statically significance difference. Lower blood pressure (both SBP and DBP), the blood cholesterol and the bloodglucose were found in "Desert people" than in controls with statically significance difference.The significantly lower prevalence of hypertension in "Desert people" was 9.94%, than in controls 29.11%, (?2=42.476, P=0.000). The incidence of ECG Left ventricle hypervotage in the "Desert people" was 33.04%, that significantly higher than in the controls 12.16%, (?2=32.443, P=0.000). The salt intake and the sodium intake in "Desert people" were statistically significantly lower than in controls.Multivariate logistic regression analysis indicated that age, the body mass index (BMI), HDL-C, LDL-C, and salt intake in diet were associated with traditional hypertension risk factors.The variants in I/D within ACEgene, C-344T and K173R within CYP11B2gene, including alleles andgenotype showed no association with the EH of "Desert people" in the Taklimakan Desert. We may speculate that the desert people has the tendency to make more mutation as T allele type carriers from T locus ingenotype of C-344T polymorphisms of CYP11B2gene in dry and hot conditions.Low BMI, few fat people and thin chest wall, T allele type carriers ingenotype of C-344T polymorphisms of CYP11B2gene are associated with left ventricle hypervoltage of "Desert people". Haplotype analysis indicated that the haplotypes T-R (C-344T and K173R within CYP11B2gene) were more prevalent in the "Desert people"group than in the controls (x2=4.898, P=0.027). The common risk factors of atherosclerosis such as EH, high bloodglucose, high cholesterol and metabolic syndrome (MS) were significantly lower in the "Desert people"group than controls (/><0.001). The "Desert people" IgM levels in serum were statistically lower than the controlgroup (t=4.781, P=0.000). The low IgM levels of "Desert people" may be associated with their low incidence of atherosclerosis.The HSP70-hom (+2437 T/C) polymorphisms of "desert people " were associated with their atherosclerosis.TTgenotype carriers within "desert people "may be the advantageous factors of their atherosclerosis.Haplotype analysis indicated that the haplotypes C-G-C (+190G/C,+1267A/G+2437T/C within HSP70gene) were more prevalent in the controls than in the "Desert people"group (P<0.05). Conclusions:The preliminary results showed that the physiological characteristics with low BMI, low blood pressure, low blood cholesterol, low bloodglucose and the ECG Left ventricle hypervotage in "Desert people". The prevalence of hypertension in "Desert people" was significantly lower than in controls which may be beneficial from their physiological characteristics and lifestyle with low salt loading, little smoking and drinking, drinking water high calcium and low magnesium.The variants in I/D within ACEgene, C-344T and K173R within CYP11B2gene, including alleles andgenotype show no association with the EH of "Desert people" in the Taklimakan Desert. We may speculate that the desert people has the tendency to make more mutation as T allele type carriers from T locus ingenotype of C-344T polymorphisms of CYP11B2gene in dry and hot conditions.The risk factors of atherosclerosis such as EH, high bloodglucose, high cholesterol and metabolic syndrome (MS) were significantly lower in the "Desert people"group than controls. The HSP70-hom (+2437T/C) polymorphisms of "desert people" were associated with their atherosclerosis.TTgenotype carriers within "desert people "may be the advantageous factors of their atherosclerosis.