Interacting contribution of the five polymorphisms in three genes of Hsp70 family to essential hypertension in Uygur ethnicity.

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.

[Alterations in gene expression of calcium handling proteins in patients with chronic atrial fibrillation].

OBJECTIVE: To discuss the role of calcium-overloading in initiation and maintenance of atrial fibrillation (AF). METHODS: The right atrial appendages were obtained from 14 patients with AF and 12 patients with sinus rhythm. The mRNA expression of proteins influencing the calcium homeostasis was measured by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and normalized to the mRNA level of glyceraldehyde-3- phosphate dehydrogenase. The left atrial diameter (LAD), mitral valvular area (MVOA), and systolic pulmonary arterial pressure were obtained by echocardiography before surgery. RESULTS: Compared to sinus rhythm group, the mRNA levels of L-type calcium channel alc, sarcoplasmic reticulum (SR), calcium adenosine triphosphatase (Ca2+ -ATPase), and ryanodine receptor type-2 (R(Y) R2) were significantly decreased (P < 0.01); the mRNA level of inositol triphosphate receptor type-1 (IP3R1) was significantly increased (P < 0.05). No changes in the mRNA expression of phospholamban and calsequestrin were observed between two groups (P > 0.05). Correlations were found between MVOA and mRNA levels of LVDC-Calc, SR Ca2+ -ATPase (r = 0.719, P = 0.004; r = 0.625, P = 0.017). The mRNA level of SR Ca2+ -ATPase was negatively correlated with LAD (r = -0.573, P = 0.032). CONCLUSIONS: Calcium loading may be responsible for the occurrence and maintenance of AF, and abnormal regulation in the mRNA expression may be the molecular mechanism of intracellular Ca2+ overload. The progressive nature of AF involves structural change.

[Comparative study of APOB gene 3'VNTR polymorphisms between natural longevity and controls in Uighur nationality].

OBJECTIVE: To investigate the association of polymorphisms in the apolipoprotein B gene (APOB) 3'variable number of tandem repeat with natural longevity in the Xinjiang Uighur nationality people. METHODS: Totally 191 healthy individuals over 90 years and 53 individuals aged 65-70 years were recruited among Xinjiang Uighur population, the nationality, gender and living area were matched. Genotyping was performed using polymerase chain reaction-sequence specific primer(PCR-SSP) and PCR-sequencing. RESULTS: Fourteen alleles were found in the Xinjiang Uighur nationality population. The frequency of HVE36 and HVE42 in the natural longevity group were significantly higher than that in the control group (both P<0.05) and HVE44, HVE46, HVE48 and HVE58 were only found in the natural longevity group. However, the frequency of HVE26, HVE30 and HVE34 were markedly lower in the natural longevity group compared to the control group. Logistic regression analyses revealed that allele L and the genotypes LL were positively associated with age, whereas the allele S and genotype SS were negatively associated with age (both P<0.05). Each allele consists of 15 bp tandem repeats with rich-AT by PCR-sequencing. CONCLUSION: These results indicate that the S allele, and SS genotype are frail factors in China Uighur natural longevity people, whereas allele L and genotypes LL are protective factors.

[Physiological characteristics and cardiac electrophysiology manifested in Minnesota coding of the "desert people" in Taklimakan Desert: study of 224 cases].

OBJECTIVE: To study the physiological characteristics and cardiac electrophysiology of the "desert people" in Taklimakan Desert, an isolated population of Uygurs. METHODS: Two hundred and twenty-four out of the 1030 "desert people", 133 males aged 37.8 +/- 17.5 (15-99) and 91 females aged 34.1 +/- 12.1 (27-85), underwent measurement of height, body weight, waist circumference, and blood pressure. Twelve-lead resting electrocardiogram was obtained and Minnesota coding was conducted. 150 Kariya Uygurs, 76 males aged 50.7 +/- 15.6 (27-85) and 75 females aged 46.6 +/- 11.7 (24-69) were used as controls. RESULTS: The abnormal Minnesota coding rate in the "desert people" as a whole was 46.0%, significantly higher than that of the controls (35.1%, P < 0.05). In the "desert people", the abnormal Minnesota coding rate was 54.9% in the males, significantly higher than that in the females (33.0%, P < 0.05). In the control group, the abnormal coding rate was 28.0% in the females and 42.1% in the males. The ECG high left R amplitude rate (code 3-1, 3-3) of the "desert people" as a whole was 32.6%, significantly higher than that of the controls (12.6%, P < 0.001). Within the "desert people" group, the ECG high left R amplitude rate of the females was 19.8%, significantly lower than that of the males (41.2%, P < 0.005). Within the control group, the ECG high left R amplitude rate of the females was 10.7%, not significantly different from that of the males (14.5%, P > 0.5). The hypertension rate of the "desert people" was 7.6%, significantly lower than that of the controls (36.4%, P < 0.005). The hypertension rate of the "desert people" coded as with left high R amplitude was 12.2%, significantly lower than that of the controls coded as with left high R amplitude (41.6%, P < 0.005). The overweight and obesity rate of the "desert people" was 9.6%, significantly lower than that of the controls (23%, P < 0.005). The arrhythmia (8-1 - 8-8) rate of the "desert people" was 8.92%, not significantly different from that of the controls (6.62%, P > 0.05). The incidence of conduction block (7-1 - 7-8) of the "desert people" was 3.12%, not significantly different from that of the controls (2.64%, P > 0.05). CONCLUSION: The higher incidence of ECG high left R amplitudes and low prevalence of hypertension in the "desert people" suggest that the high left R amplitude in "Desert people" may be related to their thin chest wall, low BMI, and physiological left ventricular hypertrophy. The "desert people" have more physical work, and less stress and pollution. They have low incidence of congenital heart disease, rheumatic heart disease and hypertension. All these may be associated with a low incidence of arrhythmia.

[Polymorphism of apolipoprotein E gene and natural longevity in the Xinjiang Uighur people: an association study].

OBJECTIVE: To explore the distribution of polymorphisms of apolipoprotein E(apoE) gene and its relation to natural longevity in the Xinjiang Uighur people. METHODS: Using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP), the authors obtained data from centenarians(n=42), 90-year-old people (n=102), 65-70-year-old people (n=70) and controls(n=53). RESULTS: The frequencies of apoE genotypes epsilon 3/4, epsilon 3/3 and epsilon 2/3 were 2.4%, 69.0% and 23.8% respectively in the centenarian group, and the frequencies of their epsilon 4, epsilon 3 and epsilon 2 alleles were 1.2%, 82.1% and 16.7%. The frequencies of genotype epsilon 3/4 and epsilon 4, epsilon 3 allele in the centenarian group were significantly lower than those in controls(P< 0.01), whereas the frequencies of genotype epsilon 2/3 and epsilon 2 allele in the centenarian group were significantly higher than those in controls(P< 0.01). Longevity was noted to be positively correlated with epsilon 2 and negatively correlated with epsilon 4. CONCLUSION: This relationship reflects a genetic influence on differential survival and may point to pleiotropic age-dependent effects on longevity.

[Polymorphism of angiotensin converting enzyme gene and natural longevity in the Xinjiang Uygur people: an association study].

OBJECTIVE: To explore the distribution of I/D polymorphisms of angiotensin converting enzyme (ACE) gene and its relation to natural longevity in the Xinjiang Uygur people. METHODS: Polymerize chain reaction, single strand conformation polymorphism, and direct sequencing technique were used to test the I/D polymorphisms of ACE gene in 42 centenarians, 102 people aged 90-99, 70 people aged 65-70, 53 cases of natural death aged 65-70 were used as controls. RESULTS: The frequencies of ACE genotypes DD, DI, and II were 28.6%, 30.9%, and 40.5% respectively in the centenarian group, the frequency rates of D and I alleles were 0.44 and 0.56. The frequency rate of D/D genotype of the centenarian group was significantly higher than that of the group aged 65-70 (28.6% vs. 12.9%, chi2 = 4.25, P < 0.05), however, not significantly different from that of the group aged 90 (P > 0.05). The frequency rate of D allele of the group of centenarian was significantly higher than that of the group aged 65-70 (44.0% vs. 36.4%, chi2 = 4.47, P < 0.05). The frequency rates of genotype D/D and D alleles were significantly higher in the centenarian group than in the controls (both P < 0.01). CONCLUSION: ACE gene polymorphism is closely correlated with life span of individuals. Longevity is the result of pleiotropic age-dependent influence of multiple factors.

Time-series analysis of systolic blood pressure variation in thirty-three Uygur centenarians in China.

The Uygur are reported to have an unusually long life expectancy. The purpose of this research was to perform a time-series analysis of systolic blood pressure (SBP) variations in the Uygur and clarify the role of blood pressure variation (BPV) in their longevity. A cross-sectional survey was carried out in Hotan. We investigated 133 clinically healthy elderly Uygur subjects and divided them into two groups: 1) 33 Uygur centenarians in Hotan (UCH; aged > or = 100 years); and 2) 100 elderly Uygur in Hotan (UEH; aged 65-70 years). Blood pressure (BP) was monitored and analyzed with ambulatory BP monitoring. The frequency domain measures were obtained with the maximum entropy method. The mean 24-h SBP was higher in UCH than in UEH. The ratio of non-dipper type BPV was larger in the UCH than in UEH. The highest power spectral density occurred over a 12-h rather than a 24-h period in both UCH and UEH. Ultradian BPVs were more frequent in UCH than in UEH. The least square-fitting curves demonstrated that the maximum values, minimum values, and mean 24-h SBP values were higher in UCH than in UEH. The higher BP and greater number of ultradian BPVs in UCH may have been due to the greater energy expenditure for maintaining daily activities in this population. Factors such as meals, daytime naps, nocturnal micturition, decreased baroreceptor sensitivity, and arterial sclerosis may also have contributed to the higher ultradian BPVs. In conclusion, BPV in the 12-h is more dominant than in the 24-h in both UCH and UEH. BPVs in the 3-h and 4-h are more frequent in UCH than those in UEH.

[Relationship of I/D polymorphism of angiotensin converting enzyme gene with hypertension in Xinjiang Kazakh isolated group].

OBJECTIVE: To investigate whether the insertion/deletion(I/D) polymorphism in the angiotensin converting enzyme(ACE) gene is associated with essential hypertension in Xinjiang Kazakh isolated population. METHODS: The study covered 201 hypertensives and 151 normotensive controls in Xinjiang Barlikun Kazakh population. The I/D polymorphism of ACE gene was determined by polymerase chain reaction. RESULTS: The frequencies of D and I in the hypertensive group (0.44 and 0.56, respectively) were not significantly different from the controls(0.39 and 0.61, respectively, P=0.16). The frequencies of ACE genotypes of DD, ID, and II were 0.18, 0.52, 0.30 in hypertensives respectively and 0.17, 0.43, 0.40 in control group respectively. There was no significant difference in genotypes between hypertensive group and normotensive group (P=0.14). CONCLUSION: The results suggested that the I/D polymorphism of ACE gene might not be associated with hypertension in the Kazakh population of Xinjiang Barlikun area.