[Show abstract][Hide abstract] ABSTRACT: In 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.
The 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.
A 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.
165 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%.
Applying 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.
PLoS ONE 01/2013; 8(12):e81806. · 3.73 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To explore the sociodemographic patterning of risk factors for cardiovascular disease (CVD) in three isolated-based subgroups of the Uyghur population in Xinjiang, China.
A cross-sectional study. Between 2005 and 2008, a non-probability sampling design method was used to select three specific groups of the Uyghur rural populations based on their potential socioeconomic status (ie, isolated, semi-isolated and open-environment status).
Three communities (named Desert, Turpan and Yuli Rob) in Southern Xinjiang autonomous region, China.
1656 people were included in this study. The inclusion criteria were that all participants were 18 years or older, they were descendants of at least three generations living in the same region, and there was no history of intermarriage.
The prevalence of CVD risk factors (ie, tobacco use, alcohol use, obesity, dyslipidemia, hypertension, diabetes, etc) was assessed.
Compared with the Desert and Turpan communities, Yuli Rob had the highest levels of obesity, dyslipidemia and hypertension, and the Desert had the lowest levels of CVD risk factors. Age standardisation slightly altered the estimates, though the patterns remained unchanged. Some unique characteristics were also found. For example, the Desert group displayed significantly lower high-density lipoprotein cholesterol (HDLC) level compared with Yuli Rob and Turpan groups. The mean values were 0.63, 1.06 and 1.45 mmol/l for men and 0.64, 1.22 and 1.51 mmol/l for women (p<0.0001). The HDLC levels in the Desert group increased with increase in body mass index and fasting glucose levels, which was inconsistent with previous studies.
Identifying the unique CVD risk factors of the ethnic-specific populations is very important in development of tailored strategies for the prevention of CVD.
[Show abstract][Hide abstract] ABSTRACT: The 'desert people' or Keriyans are able to maintain normal body functions whilst living in the hot, arid areas of Taklimakan Desert. However, little is known about the adaptive mechanisms in this extreme environment. We explored the relationship between polymorphism of C-344T in the promoter region of the aldosterone synthase gene (CYP11B2) and resting electrocardiogram (ECG) hypervoltage in this population.
The study recruited 503 Keriyans who were living in the Taklimakan Desert and 237 age/gendermatched controls from the Uighurs living in neighbouring villages. Parameters of physical fitness, ECGs, and biochemistry were compared between the two groups. The C-344T single nucleotide polymorphism (SNP) in the promoter region of CYP11B2 was genotyped by polymerase chain reaction based restriction fragment length polymorphism (PCR-RFLP) and sequencing.
The incidence of ECG left ventricular hypervoltage in the Keriyans was significantly higher than that in the controls (p < 0.001). The frequency of allele 344T was higher in this population than that in the controls (OR = 1.48; 95% CI:1.082-2.023). A higher OR for allele 344T was also seen in Keriyans with ECG left ventricular hypervoltage against those without this finding (OR = 1.557; 95% CI:1.032-2.349).
The polymorphism of C-344T in the promoter region of the CYP11B2 gene was associated with ECG left ventricular hypervoltage in the Keriyan population.
Journal of Renin-Angiotensin-Aldosterone System 02/2011; 12(3):375-9. · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Mounting evidence suggests that all organisms at the cellular level respond to stress by synthesizing heat shock proteins at the expense of other proteins, and the ability of human cells to respond to heat stress decreases with aging. We thus investigate the association of 3 variants (A1267G in HSPA1B, G190C in HSPA1A, and T2437C in HSPA1L) in the heat shock protein 70 (Hsp70) family with natural longevity in a Xinjiang Hetian Uygur population. A case-control study was conducted in 191 healthy individuals greater than 90 years of age, and 53 naturally died persons 65-70 years of age. Promoter activity was evaluated by luciferase reporter assays. The data were analyzed using an EH/EH+ program for haplotype prediction and MDR software for gene-gene interaction. All studied variants satisfied the Hardy-Weinberg equilibrium in each group. In single-locus analysis, no significant differences were found between long-lived people and short-lived people in the genotype/allele distributions of all variants. In contrast, haplotype analysis indicated that haplotypes A-G-C and A-C-T were more prevalent in long-lived people than short-lived people (P=0.026 and 0.017), and the analysis conferred a 3.46- and 4.51-fold increased tendency for longevity, respectively (P=0.025 and 0.016). The haplotype results were strengthened by interaction analysis, which suggests an optimal model in which G190C and T2437C exert an interacting effect on longevity. No functional significance was observed between 190G and 190C alleles in both control and heat-inducible A549 cells (P>0.05). Taken together, our findings suggested that common genetic variants in Hsp70 family might contribute interactively to longevity the Xinjiang Hetian Uygur population.
Translational Research 11/2009; 154(5):257-64. · 3.49 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A major mechanism of hypertension in many postmenopausal women is deficiency of female gonadal steroids. A long postmenopausal period may thus represent one factor that influences the prevalence of hypertension because of long periods of estrogen loss.
When we conducted a medical survey in northwestern China, we also asked 150 postmenopausal female subjects to provide age at menopause in a questionnaire. Age at menopause ranged from 37 to 57 years for all subjects. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) in all subjects were obtained from 24-h ambulatory blood-pressure monitoring.
An inverse correlation was identified between age at menopause and SBP and DBP, and a positive correlation was found between postmenopausal period and either SBP or DBP. Blood pressure, age at menopause, and postmenopausal period were not significantly related to body mass index, plasma renin activity, glomerular filtration rate, or urinary excretion values of sodium and potassium.
Our results clearly demonstrated that higher blood-pressure levels in postmenopausal women depend on age at menopause and postmenopausal period, but not subjects' age, suggesting that a longer absence of female gonadal steroids represents a major factor contributing to increased blood pressure in elderly women.
American Journal of Hypertension 11/2007; 20(10):1045-50. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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 that determine the physiological systems that mediate the response. The purpose of this investigation was to clarify the contributions of genetic background and lifestyle to EH through an association study using some common single nucleotide polymorphisms (SNPs) that should have functional effects on EH phenotypes. We studied the associations between common SNPs of some causal genes related to EH and lifestyle in a Japanese population. The variants of the causal genes were selected based on their functions, including: obesity (adrenergic, beta-3-, receptor: ADRB3), alcohol consumption (aldehyde dehydrogenase 2: ALDH2), water-electrolyte metabolism (guanine nucleotide binding protein [G protein], beta polypeptide 3: GNB3), glycometabolism (peroxisome proliferator-activated receptor gamma: PPARG), lipometabolism (cholesteryl ester transfer protein, plasma: CETP), atherosclerosis (5,10-methylenetetrahydrofolate reductase [NADPH]: MTHFR), and cellular behavior (gap junction protein, alpha 4, 37 kD: GJA4). Case-control association analysis showed a significant association between EH and both the ALDH2 (Lys487Glu) and GNB3 (C825T) variants. Logistic regression analysis indicated that body mass index (BMI) is an important risk factor for EH, and that the GG (Glu/Glu) genotype of ALDH2 was an independent risk factor for EH overall and especially for EH in males. There was no interaction between the ALDH2 genotype and alcohol consumption overall or in male subjects. Our results suggest that the ALDH2 genotype is associated with EH independently of alcohol consumption.
Hypertension Research 08/2007; 30(7):585-92. · 2.79 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This paper investigated the correlation between polymorphisms and haplotypes in the apolipoprotein B (apoB) gene (SP-I/D, Xbal-RFLP, VNTR) and natural longevity persons among the Uygur people in Xinjiang. For this purpose, 191 healthy Uygur individuals aged above 90 from Hetian area of Xinjiang were recruited, and another 53 persons aged 65-70 from the same nationality, the same region and with the same gender ratio, served as the control group. Genotyping was performed by PCR-SSP, PCR-RFLP and PCR-sequencing methods. Logistic regression analyses revealed that the frequencies of X+ X+ genotype, M and L alleles and the genotypes composed of M and L were significantly higher in the longevity group than in the control group. In haplotype analyses, we found that, in the long-lived people, the frequency of haplotypes composed of the X+ and M alleles was significantly higher whereas the frequency of haplotypes composed of the X-and S alleles was significantly lower (both P<0.05) I than those of their controls. These results indicated that the S allele, SS genotype and X+-S, D-S, D-X+-S haplotypes were the possible adverse factors, whereas the M, L alleles, X+X+, MM, ML, LL genotypes and I-X+-M, X+-M haplotypes were the possible protective factors for the naturally long-lived Uygur people in China.
Science in China Series C Life Sciences 02/2007; 50(1):80-7. · 1.61 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To study white coat (WC) hypertension in centenarians, a cross-sectional surveillance was carried out on Uygurs, a long-lived population in China.
Twenty-four-hour ambulatory blood pressure (BP) monitoring (ABPM) was performed in 33 centenarians (age range, 100 to 113 years) and compared with 100 elderly subjects (age range, 65 to 70 years). All subjects were clinically healthy and capable of self-care. Subjects had no history, signs, or symptoms of cardiovascular disease and were receiving no medical treatments. Office BP, 24-h mean, daytime and night-time BP, pulse pressure, heart rate, standard deviation (SD), and coefficient of variation (CV) of the same variables were extracted from ABPM. The WC effect was defined as the difference between mean office and daytime BP.
Centenarians demonstrated higher prevalence of WC hypertension, compared to elderly group (15% vs. 5%). The WC effect was also greater in centenarians than in elderly subjects, and was more marked for systolic BP than for diastolic BP and heart rate. The WC effect for systolic BP was positively correlated with both SD (r = 0.45, P < .01) and CV (r = 0.55, P < .01) for 24-h systolic BP in centenarians, but not in elderly subjects.
Prevalence of WC hypertension was greater in centenarians than in elderly subjects. The WC effect and BP variation may be increased in centenarians. Previously observed higher BPs seen in very elderly individuals might be explained by the greater impact of WC hypertension.
American Journal of Hypertension 08/2005; 18(8):1040-5. · 3.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Cross-sectional surveillance was carried out in long-lived Uygur in China to investigate blood pressure (BP) and pulse rate (PR) variation in centenarians. The study group comprised 33 centenarians (age > or = 100 years), 103 longevous subjects (age 90-99 years) and 100 elderly (age 65-70 years) subjects. Office BP was measured, and 24-h noninvasive ambulatory blood pressure monitoring (ABPM) was performed. The office BP was higher and hypertension occurred more frequently in the centenarians than in either the longevous or elderly subjects. Mean 24-h systolic and diastolic BP was higher in the centenarians than in the other 2 groups. However, mean 24-h PR did not differ between them. Day-night differences in systolic BP decreased, and the non-dipper-type BP pattern was common in the centenarians (79.1% vs 68% and 63.6% in longevous and elderly subjects, respectively). Circadian BP was characterized by 3 peaks in longevous subjects and multiple peaks in centenarians. Morning rising and nocturnal dipping of BP were observed in both longevous and elderly subjects. In conclusion, BP in longevous and elderly Uygur was characterized by circadian rhythmicity, but the nocturnal fall in BP was not seen in centenarians. Differences in day-night BP and circadian rhythmicity may decrease with advancing age, especially in centenarians.
[Show abstract][Hide abstract] ABSTRACT: The purpose of this study was to clarify the relationship between blood pressure variation and urinary catecholamines in longevous people.A cross-sectional observational study was conducted on 260 elderly subjects in Xinjiang, China. All of subjects were divided into three groups. 1. Longevous Uygur group: (103 subjects, age > 90years); 2. Elderly Uygur group: (107 subjects, aged 65-70 years); 3.Elderly Han group: ( 50 subjects aged 65-70 years). Blood pressure (BP) and pulse rate (PR) were monitored every 30min for more than 26 hours using ambulatory blood pressure monitors(ABPM). Office and mean 24- hr BP, PR were analyzed in each group with conventional statistics. Urinary catecholamines were measured HPLC-DPE methods.1. ABPM has shown that the prevalence of hypertension is lower in longevous group than other elderly groups (P>0.001). 2. White coat effect is common in the longevous groups. 3. The ratio of dipper type were 52 % in longevous Uygur group, 51%in elderly Uygur group and 45% in elderly Han group. 4.Urinary norepinephrine (NE) and dopamine(DA) concentrations were not different among the three groups. However, urinary epinephrine (E) concentrations in elderly Han group higher than the other groups (Elderly Han group 6.8±7.8μg/day, Longevous Uygur group 4.2±2.7μg/day, Elderly Uygur group 3.8±2.0μg/day, p>0.05).In summary, dipper type variation of normotentive blood pressure and lower urinary epinephrine concentrations may be one of the important factors in longevity.
American Journal of Hypertension - AMER J HYPERTENS. 01/2001; 14(4).