The vitamin D status among Tibetans.

UVB from the sun and intake from food are the only human sources of vitamin D. Tibet is a unique region for comparisons of these sources: (1) it lies at a low latitude and at a high altitude and has very large annual fluences of UVB; (2) the traditional Tibetan food is poor in vitamin D. Blood samples were taken from 63 persons of different age, with different occupations and staying at different places. UVB doses at these places were measured. The samples were analyzed by a standard radioimmune assay for determination of the serum concentration of 25 hydroxyvitamin D (25(OH)D). The main finding was that among nomads, there seems to be severe vitamin D deficiency (serum levels of 25(OH)D<30 nM). We tentatively propose that the low level of 25(OH)D of nomads is related to their clothing and sun exposure habits. For persons of other occupations (students, teachers and farmers) the levels are higher, although a significant fraction of these persons also have lower levels than 75 nm, by many regarded as a limit for insufficiency related to a number of negative health conditions. The annual dose of vitamin D-generating UVB is about five times larger in Lhasa than in Oslo. Despite this, the average vitamin D status seems to be similar, except in the case of nomads. This phenomenon is certainly related to food habits. In conclusion, the 25(OH)D status among nomads in Tibet appears to be alarmingly low. However, for people of other occupations the status is more normal.

Genetic polymorphisms of angiotensinogen and essential hypertension in a Tibetan population.

The human angiotensinogen gene (AGT) is a promising candidate for an essential hypertension-susceptibility gene. We aimed to explore the single-locus, haplotype and epistasis patterns of three polymorphisms of AGT (A-20C, A-6G and M235T) and their relation to the risk of essential hypertension in a Tibetan population. The three polymorphisms were genotyped in 333 essential hypertension patients and 235 healthy controls on the basis of a door-to-door cross-sectional study. Genotyping was performed using polymerase chain reaction (PCR)-restriction fragment length polymerase (RFLP) and direct sequencing techniques. The data were analyzed using the EH/EH+ program and the multifactor dimensionality reduction (MDR) method. Our single-locus analysis revealed that except for a marginal, significant association of A-20C allele distribution, no significant association between genotype and allele distributions of the A-20C, A-6G, or M235T polymorphism of AGT and essential hypertension was found. In haplotype analysis, we found that the H(1) haplotype may be the risk-conferring factor for hypertension, even after the Bonferroni correction. In epistasis analysis, we selected the final best model, which included the A-20C and A-6G polymorphisms with a strong synergistic effect. This model had a maximum testing accuracy of 0.564 and a maximum cross validation consistency of 10 out of 10 (p=0.001). The present study thus provides evidence of a strong synergistic effect of the A-20C and A-6G polymorphisms of AGT, which were not found to be associated with essential hypertension in the single-locus analysis. Moreover, we have proposed a promising data-mining analytical method using the open-source MDR software package for detecting and characterizing gene-gene interactions.

[A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations].

OBJECTIVE: To clarify whether A1166C polymorphism of the angiotensin II type 1 receptor (AT(1)R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. METHODS: This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in genomic DNA. The data were analyzed by ANCOVA, chi-square test, and multiple logistic regression. RESULTS: In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (chi-square=4.166, P=0.125). The frequency of the A1166 allele in Tibetan male hypertensives was significantly higher than that in normotensives (chi-square=11.46, P=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (P=0.465) or Yi (P=0.357) populations. Body mass index in the Han and Yi populations (P=0.0001), age in the Tibetan and Yi populations (P=0.0001), and AA genotype in the Tibetan male population (P=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (P=0.0040). CONCLUSION: The A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT(1)R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT(1)R gene is probably not involved in the pathogenesis of essential hypertension in Han and Yi populations.

A1166C polymorphism of the angiotensin II type 1 receptor gene and essential hypertension in Han, Tibetan and Yi populations.

Our aim was to clarify whether substitution of cytosine for adenine at position 1166 (A1166C) polymorphism of the angiotensin II type 1 receptor (AT1R) gene is associated with susceptibility to essential hypertension in Han, Tibetan and Yi populations in China. This study involved 302 normotensive and 446 hypertensive subjects. The polymorphism was detected by polymelase chain reaction of genomic DNA and restriction fragment length polymorphism (PCR-RFLP) in genomic DNA. The data were analyzed by analysis of covariance (ANCOVA), X2 test, and multiple logistic regression. In normotensive controls, the A1166 allele frequencies were 0.979, 0.939 and 0.965 in Han, Tibetan and Yi participants, respectively. There was no significant intergroup variation in frequency of the allele in normotensives (X2=4.166, p=0.125). The frequency of the A1166 allele was significantly higher in Tibetan male hypertensives than that in normotensives (X2=11.46, p=0.001). There was no significant difference in A1166C genotype distribution and allele frequency between normotensives and hypertensives either in the Han (p=0.465) or Yi (p=0.357) populations. Body mass index in the Han and Yi populations (p=0.0001), age in the Tibetan and Yi populations (p=0.0001), and AA genotype in the Tibetan male population (p=0.0034) all were independent risk factors for hypertension. Diastolic blood pressure levels were significantly higher in Tibetan male subjects with the AA genotype than in those with the AC+CC genotype (p=0.0040). We concluded that the A1166 allele is very common in Han, Tibetan and Yi populations, approximately 1.35-fold more common than in Caucasians. The A1166 allele of the AT1R gene may be a predisposing factor for essential hypertension in Tibetan males. A1166C polymorphism of the AT1R gene is probably not involved in the pathogenesis of essential hypertension in Han or Yi populations.

Angiotensin-converting enzyme gene polymorphism and its association with essential hypertension in a Tibetan population.

There is strong evidence to support the idea that the renin-angiotensin system (RAS) plays an important role in the pathogenesis of essential hypertension (EH) and its complications. However, existing data about the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism with blood pressure is conflicting, mainly due to racial differences and environmental exposure status. We therefore conducted a case control study to observe the relationship between ACE I/D polymorphism and EH in a Tibetan population who live in relatively isolated areas and are genetically homogeneous. The study was conducted at stable residential communities in the urban district of Lhasa, the capital of the Tibet autonomous region, China, and 106 unrelated EH patients and 135 normotensIve subjects were recruited. PCR, PCR/RFLP and PCR-SSCP were carried out to study the association between RAS genes and EH. Frequencies for the DD, ID and II genotypes were 27, 47 and 29 in hypertensive subjects, and 15, 60 and 48 in normotensive subjects, respectively. Derived allele frequencies for the I and D alleles were 0.51 and 0.49 in hypertensive subjects and 0.64 and 0.36 in normotensive subjects. There were significant differences in genotype distribution and derived allele frequency between these two groups. The genotype and allele frequencies of the ACE gene differed significantly between hypertensive and normotensive females (p>0.05), but there were no differences in males. In females, the DBP and MAP level were significantly higher for the DD than for the ID and II genotype, and SBP was significantly higher for the DD than for the II genotype. But in males, there were no significant differences in blood pressure among ACE genotypes. The results showed a significant association between the D allele of the ACE gene and hypertension in Tibetan women but not in Tibetan men.