Association of CLCNKB haplotypes and hypertension in Mongolian and Han populations.

We investigated a possible association between genetic variations in chloride channel Kb (CLCNKB) gene and essential hypertension (EH) in the Mongolian and Han populations in Inner Mongolia. Our study included 414 unrelated Mongolian herdsmen and 524 Han farmers. Two tagSNPs of CLCNKB (rs945393 and rs10803414) 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. There was significant difference in allele frequency of rs10803414 between the EH group (35%) and the control group (26%) in the Mongolian population (P < .05). Significant association was identified between rs10803414 and EH in the Mongolian population (P < .05) and rs945393 and EH in the Han population (P < .01). The frequency of haplotype CC in the EH group (9.4%) was significantly higher than in the control group (4.6%) in the Mongolian population; individuals who possessed the CC haplotype had a significantly higher risk of EH in the Mongolian population. There was no association between haplotype and EH in the Han population. After adjusting for age, sex, and other confounding risk factors, only rs10803414 was the risk factor of hypertension in Mongolians. Our results indicate that rs10803414 in CLCNKB confers a significant risk of EH in the Mongolian population and haplotype CC of CLCNKB is a genetic factor for EH in the Mongolian population. Our study expands the association between CLCNKB and EH to a non-European ancestry population and provides the first evidence of a cross-race susceptibility of EH locus.

ADD1 Single Nucleotide Polymorphisms Are Associated With Essential Hypertension Among Han and Mongolian Population in Inner Mongolia Area.

Aldosterone synthase (CYP11B2) and α-adducing (ADD1) are candidate genes that play key roles during essential hypertension (EH) incidence. However, the association between their genetic mutations and the risk of EH is unclear. The present study investigated specific single nucleotide polymorphisms (SNPs) from CYP11B2 and ADD1, and their potential role as risk factors for EH based on 423 Mongolian and 410 Han people in Inner Mongolia province. In the allelic model, people with ADD1 rs2239728-A presented a 0.74-fold risk than rs2239728-C, whereas the ADD1 rs4961-T was associated with a 1.37-fold higher risk than allele G in the Han population. The genetic model reported that the rs2239728-A carrier (AA + AC) was 0.59-fold lower than the CC carrier, whereas the rs4961-G carrier (GG + GT) was 0.59-fold lower than the TT carrier in the dominant model. After gender adjustment, people with rs2239728-A was a 0.63-fold risk than -C in EH, but the rs4961-T carrier was associated with a 1.63-times higher risk than -G in females. Haplotype analysis showed that GCCT was associated with essential hypertension in the Han population, and it was a risk factor for EH. Our identification reported novel SNPs of ADD1 with protective significance for EH among females in the Chinese Han population, together with its haplotype GCCT as a risk factor for EH.

Variants in the 3' End of SLC6A3 in Northwest Han Population with Parkinson's.

Parkinson's disease (PD) is one of the most common neurodegenerative disorders in neurology. It is possible that multifactorial and genetic factors are related to its pathogenesis. Recently, there have been reports of SLC6A3 genetic variants leading to PD. However, the role of 3' end of SLC6A3 in PD is less studied in different ethnic groups. To explore the roles of 3' end of SLC6A3 in PD development, 17 SNP sites in 3' end of SLC6A3 were analyzed in 360 PD patients and 392 normal controls of Han population residing in northwest of China. The significant difference of gene type and allele frequencies between the PD and control groups was detected only in rs40184 (P = 0.013 and 0.004, respectively; odds ratio 2.529, 95% confidence interval 1.325-4.827). The genotype and allele frequencies of the other 16 SNP sites were not found to be different between the PD group and the control group. rs2550936, rs3776510, and rs429699 were selected to construct the haplotypes; no significant difference was found in a frequency of 5 haplotypes between the PD group and the control group. These results suggest that the SLC6A3 variant in rs40184 A allele may increase the risk of PD in northwest Han population and may be a biomarker of PD.

Multi-generational impacts of arsenic exposure on genome-wide DNA methylation and the implications for arsenic-induced skin lesions.

As a nonmutagenic human carcinogen, arsenic (As)'s carcinogenic activity is likely the result of epigenetic changes, particularly alterations in DNA methylation. While increasing studies indicate a potentially important role for timing of As exposure on DNA methylation patterns and the subsequent differential risks for As toxicity and carcinogenesis, there is a lack of research that tackles these critical questions, particularly in human based populations. Here we reported a family-based study including three generations, in which each generation living in the same household had a distinctive timing of As exposure: in adulthood, in utero and during early childhood, and in germlines exposure for grandparents, parents, and grandchildren, respectively. We generated genome-wide DNA methylation data for 18 As-exposed families, nine control families, as well as 18 arsenical skin lesion patients. Our analysis showed that As exposure may leave detectable DNA methylation changes even though exposure occurred decades ago, and the most significant changes of global DNA methylation were observed among patients afflicted with arsenical skin lesions. As exposure across generations shared common differentially methylated DNA loci and regions (744 DML and 15 DMRs) despite the distinctive exposure timing in each generation. Importantly, based on these DML, clustering analysis grouped skin lesion patients together with grandparents in exposed families in the same cluster, separated from grandparents in control families. Further analysis identified a number of DML and several molecular pathways that were significantly distinguished between controls, exposed populations, as well as skin lesion patients. Finally, our exploratory analysis suggested that some of these DML altered by As exposure, may have the potential to be inherited affecting not only those directly exposed but also later generations. Together, our results suggest that common DML and/or DMRs associated with an increased risk for disease development could be identified regardless of when exposure to As occurred during their life span, and thus may be able to serve as biomarkers for identifying individuals at risk for As-induced skin lesions and possible cancers.

Associations SELE gene haplotype variant and hypertension in Mongolian and Han populations.

UNLABELLED: Genetic variation is thought to contribute to the etiology of hypertension, and E-selectin is a candidate essential hypertension-associated gene. OBJECTIVE: In this study, we attempted to test the hypothesis that subtle haplotype variants of SELE genes may be sources of essential hypertension in Mongolian and Han populations. MATERIALS: A total of 429 unrelated Mongolian herdsmen and 416 Han farmers were enrolled, including 212 Mongolian essential hypertension (EH) patients, 217 Mongolian normotensives (controls), 200 Han EH patients and 216 Han normotensives (controls). METHODS: All nine tag single-nucleotide polymorphisms (SNPs) within the SELE gene were retrieved from HapMap and the genotyping was performed using a polymerase chain reaction (PCR)/ligase detection reaction assay. Results The distributions of the A-allele frequency of rs3917458 and the C-allele frequency of rs2179172 differed significantly between the hypertensive subjects and controls in the Han population. The frequency of haplotype GGC was significantly higher in the EH group than in the controls in the Mongolian population. In the Han population, a significant difference was observed in the haplotype frequency of TCC between the patients and controls, whereas haplotype ACA was detected significantly less often in the EH subjects than in the controls. CONCLUSION: Meanwhile, the haplotype TCC in the Han hypertensive patients and the haplotype GGC in the Mongolian patients had independent effects in increasing the risk for EH and maybe used as risk factors for predicting high blood pressure. However, the haplotype ACA had an independent effect in decreasing the risk of hypertension and may be protective in normotensive subjects in the Han population. Therefore, multiple SNPs in combination in SELE may confer a risk of hypertension.