Association of SNPs in the PPARγ gene and hypertension in a Mongolian population.

The association of single nucleotide polymorphisms (SNPs) in PPARγ with hypertension is controversial. The aim of the present study was to clarify the contributions of PPARγ genetic variants to hypertension through an association study. A total of 414 unrelated Mongolian herdsmen and 524 Han farmers were included in this study. Fourteen intronic SNPs were analyzed and genotyped using a polymerase chain reaction/ligase detection reaction assay. Prior to correction for multiple testing, the SNPs rs6802898 and rs12633551 were significantly associated with the prevalence of hypertension in the Han and Mongolian populations, respectively. The genetic association of each SNP with hypertension was individually tested using logistic regression. The SNP rs6802898 was associated with hypertension in both dominant (P = 0.033) and additive models (P = 0.026) in the Han population, whereas the SNP rs12633551 was associated with hypertension in both dominant (P = 0.014) and additive models (P = 0.0073) in the Mongolian population. Moreover, SNP rs12633551 had a significant effect on systolic and diastolic blood pressure response. However, none of these associations were statistically significant after Bonferroni correction for multiple testing, although there was a significant difference among the haplotypes in the Han and Mongolian populations. Interestingly, there was an association of the PPARγ haplotypes with hypertension even after Bonferroni correction. Thus, determination of the PPARγ haplotypes in different populations may prove informative for assessment of the genetic risk for hypertension.

Association between PDCD1, CTLA4, and MECP2 gene polymorphisms and systemic lupus erythematosus in the Chinese Northern Han.

Systemic lupus erythematosus (SLE) is an autoimmune disease that results in chronic inflammation of different organ systems. Several susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes has yet to be determined. The programmed cell death 1 gene (PDCD1), the cytotoxic T-lymphocyte-associated protein 4 (CTLA4) gene, and the methyl-CpG-binding protein 2 gene (MECP2) are considered to be the candidate genes associated with SLE. We analyzed the role of PDCD1, CTLA4, and MECP2 gene polymorphisms in Han patients suffering from SLE. Using a case-control study, 263 SLE patients and 263 healthy controls were collected from Chinese Northern Han people. Genomic DNA was prepared from peripheral blood leukocytes and the genotyping was performed using a polymerase chain reaction/ligase detection reaction assay. A statistically significant difference was observed in the rs2239464 and rs2075596 polymorphisms of MECP2 between SLE subjects and controls. The GG genotype in rs2239464 and the GG genotype in rs2075596 might protect against SLE. In contrast, no such association was found in the CTLA4 or PDCD1 polymorphisms. The rs2239464 and rs2075596 polymorphisms of MECP2 might play a significant role in the development of SLE in the Northern Han of China.

Association of regulator of G protein signaling (RGS5) gene variants and essential hypertension in Mongolian and Han populations.

Genetic variants of the RGS5 gene are believed to be risk factors for hypertension and cardiovascular diseases. In this study, we investigated the association between RGS5 gene variants and hypertension in the Mongolian and Han populations. Peripheral blood was obtained from 429 unrelated Mongolian herdsmen and 416 Han farmers [including essential hypertension (EH) patients and controls]. Nine tagSNPs within the RGS5 genes were retrieved from HapMap, and the samples were individually genotyped using the polymerase chain reaction/ligase detection reaction assay. The distribution of the allele frequency of rs12035879 differed significantly between hypertensive subjects and controls in the Han population, while the distribution of the allele and genotype frequencies of rs16849802 differed significantly between hypertensive subjects and controls in the Mongolian population. We observed an association between rs16849802 and EH in the Mongolian population. The frequency of haplotype GAA was significantly higher in the EH group than in controls in the Mongolian population. However, the EH group and controls did not differ significantly in all 6 haplotypes in the Han population. The rs16849802 and haplotype GAA independently increased the risk of EH in Mongolian patients, and may be used as a risk factor for the prediction of high blood pressure.

Association of NPRA and NPRC gene variants and hypertension in Mongolian population.

NPRA and NPRC are candidate susceptibility genes for essential hypertension (EH) and play a key role in the regulation of plasma levels and biological effects of natriuretic peptides. The aims of the present study were to find new genetic markers in the NPRA and NPRC genes and to assess relationships between variants and EH. A total of 797 unrelated Mongolian herdsmen were enrolled, including 389 EH patients and 408 normotensive controls. Genotyping was performed using the polymerase chain reaction/ligase detection reaction assay. The distribution of the T-allele frequency of rs1847018 in NPRC differed significantly between hypertensive subjects and controls. There was an association between rs1847018 and EH in the additive model in NPRC (P < 0.05). There were no significant differences in the genotype and allele frequency distributions for any of the 3 single nucleotide polymorphisms in NPRA between EH and normotensive individuals. In NPRA, the frequency of haplotype TCA in the EH group was significantly lower than in controls, while the frequency of haplotype TCG was significantly higher in the EH group than in controls; Individuals who possessed the TCA haplotype had a significantly lower risk of EH, whereas the presence of haplotype TCG was significantly associated with a higher risk of EH. However, there was no significant difference between the EH group and controls in any of the 8 haplotypes in NPRC. Rs1847018 is a genetic marker of EH in NPRC, and the frequency of haplotype TCA and TCG in NPRA is associated with EH in the Mongolian population.

Association of TSC gene variants and hypertension in Mongolian and Han populations.

We investigated a possible association between genetic variations in the thiazide-sensitive Na-Cl cotransporter (TSC) gene and essential hypertension (EH) in the Mongolian and Han ethnic groups in Inner Mongolia. Our study included 385 unrelated Mongolian herdsmen and 523 Han farmers. Nine tagSNPs of TSC were identified from the Chinese HapMap database based on pairwise r(2) ≥ 0.5 and minor allele frequency ≥0.05. Genotyping was performed using the PCR/ligase detection reaction assay. Association between tagSNPs and hypertension was investigated under the additive model. There were significant differences between the genotype and allele frequencies of rs13306673 between the EH group and the control group in the Han population. Significant associations were found between the rs7204044 variant and EH in both the Mongolian and Han ethnic groups. The frequency of haplotype GCA in the EH group was significantly higher than in the control group in the Mongolian population. In the Han population, the frequency of haplotype TGG was significantly higher in the EH group than in controls, whereas haplotype TGA occurred significantly less often in EH than in controls. We suggest that rs7204044 of TSC is a genetic factor for EH in these two ethnicities and that rs13306673 is a genetic factor for EH in the Han population.

Lack of association of variants of the renal salt reabsorption-related genes SLC12A3 and ClC-Kb and hypertension in Mongolian and Han populations in Inner Mongolia.

Abnormalities in renal sodium chloride and water reabsorption play important roles in the development of hypertension. Mutations in the genes involved in renal sodium chloride reabsorption can affect blood pressure. Recently, the R904Q variant of the sodium/chloride transporters, member 3 (SLC12A3) gene and the T481S variant of the chloride channel Kb (ClC-Kb) gene were found to be implicated in essential hypertension. We investigated a possible role of the SLC12A3 and ClC-Kb genes in the prevalence of essential hypertension in the Mongolian and Han ethnic groups. The study population comprised 308 unrelated Mongolians with essential hypertension, 271 Mongolian normotensives, 285 unrelated Han with essential hypertension, and 194 Han normotensives living in Inner Mongolia. The presence of the SLC12A3 R904Q and ClC-Kb-T481S polymorphisms was determined using TaqMan PCR. The risk factors for hypertension were age, body mass index, alcohol consumption, total plasma cholesterol, and low-density lipoprotein cholesterol. The genotype and allele frequencies of SLC12A3 R904Q and ClC-Kb-T481S were not significantly different between hypertensive patients and controls in the Mongolian (SLC12A3 R904Q, P = 0.471 and P = 0.494, ClC-Kb-T481S, P = 0.960 and P = 0.960, respectively) and Han (SLC12A3 R904Q, P = 0.765 and P = 0.777, ClC-Kb-T481S, P = 0.100 and P = 0.103, respectively) populations. There was no significant association between the SLC12A3 R904Q variant and the ClC-Kb-T481S variant and essential hypertension in either ethnic group.