Essential hypertension (EH) is a multifactorial disorder determined by the interaction of environmental and genetic factors. EH patients' responses to these factors may vary, depending on differences in their genes

Experimental evidence suggesting that heat shock protein 70 (Hsp70) gene or associated genes are responsible for the pathophysiology of hypertension is accumulating. In this study, we focused on five polymorphisms in three genes (HSPA1A, HSPA1B, and HSPA1L) of Hsp70 family to explore the genetic contribution, alone and in combination, of these polymorphisms to essential hypertension risk in a Uygur population. Genotyping was performed using PCR-RFLP and direct sequencing techniques. Data were analyzed using haplotype and multifactor dimensionality reduction (MDR) methods. Genotype distributions of all the polymorphisms satisfied the Hardy-Weinberg proportions in cases and controls. Statistical significance was only observed in the genotype (P=0.0028) and (P=0.0146) allele distributions of −110A/C polymorphism, with the −110C allele conferring a 1.45-and 2.83-fold of relative risk, assuming the additive and recessive models, respectively, and in 1267A/G genotype distribution (P=0.0106) with the 1267G allele conferring a 44% reduced risk. The interaction information analysis indicated that polymorphisms −110A/C and 1267A/G had a strong synergistic effect, while polymorphisms 2074G/C and 2437T/C had a moderate synergistic effect. Haplotype analyses further strengthened the interaction information. Using the haplotype H 1 as a reference, haplotype H 4 had a 40% reduced risk, while haplotypes H 5 and H 8 had a significantly 5.00-and 3.75-fold increased risk for essential hypertension, respectively. Taken together, our results supported strong genetic interaction of the studied polymorphisms with the risk of having essential hypertension in Uygur ethnicity. Functional studies are warranted to confirm or refute these findings. This is the first study to evaluate the genetic interaction information of the Hsp70 in Uygur ethnicity, which represents one of the major nationalities in China with high homogeneity and unique lifestyles. Moreover, we employed the haplotype and MDR methods to explore the potential interaction of Hsp70 genetic polymorphisms in the pathogenesis of essential hypertension in Uygur.

t has been shown that the humans living to a very old age have a genetic tendency toward moderate and balanced blood pressure (BP). 1,2 The Uygurs in Xinjiang are a naturally longevous population, surviving to a very old age without any medical treatment or services. There have been studies showing that the Uygur people do live to an older age than other people in the Xinjiang Uygur Autonomous Region of China, 3,4 but these reports have not provided information on the blood pressure (BP) variations, such as the day -night BP differences and the circadian rhythm, in the Uygur centenarians.Noninvasive 24-h ambulatory blood pressure monitoring (ABPM) devices are now commercially available and are often used to overcome the 'white-coat' effect and identify white-coat hypertension when studying the circadian rhythm of BP. A person's ambulatory BP measured during daily life can provide more meaningful information than can recordings of BP taken in the physician's office, and interesting information is provided when this method is used for persons of different ethnicities. Therefore we used ABPM in our study of office and ambulatory BP, pulse rate (PR), prevalence of hypertension, difference between day-and night-time BP and PR, and circadian BP and PR rhythms in Circulation Journal Vol.66, January 2002 centenarian, longevous, and elderly Uygurs. Methods Study PopulationTwo hundred and thirty-six clinically healthy subjects were recruited from Uygur residences by randomized, parallel-design sampling in Hotan, Xinjiang Uygur Autonomous Region, People's Republic of China during July and August 2000. All subjects gave their informed consent to participate. Subjects were divided into 3 groups according to age: a centenarian group (33 subjects, age ≥100 years), a longevous group (103 subjects, age 90-99 years) and an elderly group (100 subjects, age 65-70 years). Elderly and longevous subjects were engaged in physical labor, despite advancing age, but the centenarians only managed their daily physical activities. We confirmed the age of subjects through resident registration forms, and marital, family and personal histories conveyed in the local language. The office BP examination was undertaken at the local hospital. All subjects resided in a dormitory of the health-care center of the village for the 3 days of this investigation. Twentyfour-hour ABPM was conducted in each subject's place of residence and they were asked to maintain their normal schedule of activity and regular rest. A diary of their activities was recorded during the BP monitoring. All subjects were served their usual meals at 07.00, 11.30, and 19.00 h. Subjects underwent other physical examinations after the ABPM ceased. None of the subjects had previously received antihypertensive agents. Office BP and 24-h BP/PR MonitoringThe office BP was determined at the beginning of the Ambulatory Blood Pressure Monitoring in Uygur CentenariansMedet Jumabay, MD; Yukio Ozawa, MD; Hiroshi Kawamura, MD*; Satoshi Saito, MD; Yoichi Izumi, MD; Hiromi Mitsubayashi, MD*...

Our findings demonstrate that genetic defects in AGTR2 and apelin genes by themselves may play an independent leading role in determining susceptibility to hypertension in both genders.

BackgroundIn centenarian populations, application of the positive biology approach (examination of positive phenotypes in aging) has revealed that mitochondrial DNA (mtDNA) mutation accumulation may be linked to human longevity; however, the role of guanine nucleotide-binding protein (G protein) abnormalities modulated by G-protein beta-3 (GNB3) and nitrate (NO2) production associated with endothelial nitric oxide synthase (eNOS), commonly appearing in age-related diseases, remains undetermined.ObjectiveThe association between the mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS polymorphisms and longevity in a Uygur population (Xinjiang region, China) were investigated.MethodsA total of 275 experimental subjects aged ≥100 or with 4 generations currently living were screened for inclusion in the centenarian (>100 years) and nonagenarian groups (90–100 years), and 112 65–70 year old control subjects were selected. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to examine mtDNA 5178A/C, mtDNA 10398A/G, GNB3 C825T, and eNOS. Associations between polymorphic loci, genotypes, and longevity were analyzed.Results165 included subjects (M∶F = 107∶58; mean age = 97±3 years; mean age 100–113 years) were assigned to the centenarian (M∶F = 46/19; n = 65) and nonagenarian groups (M∶F = 61/39; n = 100). Associations between mtDNA C5178A and A10398G polymorphisms with longevity in the centenarian group with mtDNA genotype frequencies 5178A and 10398G were 66.79% and 36.8%.ConclusionsApplying the overwhelming longevity observed in Uygur populations, these findings demonstrate that mtDNA 5178A/C and 10398A/G, GNB3 C825T, and eNOS polymorphisms are useful as a genetic basis for longevity.