Association of variants in renal salt reabsorption-related gene SLC12A3 with essential hypertension in a Mongolian population

Liang, Junqing; Xi, Yaguang; An, Chen; Su, Xiulan

doi:10.4238/2015.august.21.9

Cited by 3 publications

(5 citation statements)

References 21 publications

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“…We observed an elevated serum LDL-c level in hypertensive patients [ 21 , 23 ] when we investigated the association between genetic variants of SLC12A3 and hypertensive patients in Mongolians in China. The results from this randomly selected Mongolian sample were consistent with our hypothesis that SLC12A3 polymorphisms may modulate serum LDL-c level and represent a close relationship with hypertensive patients that have been reported previously [ 22 , 23 ]. Two SNPs (rs5803 and rs711746), which were reportedly associated with hypertension in case-control and family-based association studies, also showed significant influences on individuals’ serum LDL-c level in the general Mongolian population.…”

Section: Discussionsupporting

confidence: 92%

“…The genotyping was performed as described previously [ 22 ]. In brief, 1) the target DNA sequences were amplified using a multiplex PCR method in a final volume of 10 μl; 2) thermal cycling was performed for all SNPs loci in Gene Amp PCR system 9600 (PerkinElmer, Waltham, MA, USA); and 3) the fluorescent products of ligase detection reaction were differentiated by Applied Biosystems 3730 DNA Analyzer (Applied Biosystems, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

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SLC12A3 variants modulate LDL cholesterol levels in the Mongolian population

Zhang

2017

Lipids Health Dis

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BackgroundAbnormalities in lipid metabolism are crucial factors in the pathogenesis of cardiovascular disease (CVD). Variants of many genes have been verified to confer risk for lipid metabolism abnormalities. However, the relationship between genetic variants of the NCC-encoding SLC12A3 gene and lipid metabolism in the Mongolian population remains unclear. In the present study, we aimed to elucidate the effects of SLC12A3 variants on Mongolian lipid metabolism, including total cholesterol (TCHO), triglycerides (TG), low-density lipoprotein cholesterol (LDL-c), and high-density lipoprotein cholesterol (HDL-c).MethodsA randomly selected population of Mongolians (n = 331) from China underwent clinical testing. An ANOVA test, Kruskal-Wallis H test (K-W test) and haplotype analysis were used to evaluate the association between the levels of lipids (TCHO, TG, LDL-c, and HDL-c) and polymorphisms in SLC12A3 loci.ResultsWe identified three single nucleotide polymorphisms (SNPs) rs5803, rs2010501 and rs711746 in the SLC12A3 gene that were significantly associated with an individual’s serum LDL-c level. Haplotypes combining these SNPs also showed the same trend (all p values < 0.01). Furthermore, the influence of SLC12A3 genetic polymorphisms on differences in individual serum LDL-c levels remained significant, even after we controlled gender, and demographic and other non-genetic factors.ConclusionThese results suggest that variants of the SLC12A3 gene confer susceptibility to the abnormal serum LDL-c level in the Mongolian population.

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Section: Discussionsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

SLC12A3 variants modulate LDL cholesterol levels in the Mongolian population

Zhang

2017

Lipids Health Dis

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“…In addition, studies in Japanese patients have shown that individuals carrying the heterozygous L858H mutation have significantly different serum potassium levels from those who do not (Naraba et al, 2005). It has even been proposed that heterozygous mutations or polymorphisms in the SLC12A3 gene might significantly affect blood pressure levels (Tago et al, 2004;Liang et al, 2015). In this study, Patient #6 carried the heterozygous L671P mutation, which had not been previously reported.…”

Section: Discussionmentioning

confidence: 48%

Clinical and genetic analyses of Chinese patients with Gitelman syndrome

Miao¹,

Zhao²,

Xl³

et al. 2016

Genet. Mol. Res.

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ABSTRACT.To evaluate the genotype-phenotype relationship of Gitelman syndrome in Chinese patients. We selected patients with Gitelman syndrome presenting hypokalemia. Medical history, clinical manifestations, laboratory test results, and imaging data of these patients were collected for analysis. Target gene sequencing was performed to evaluate the genotype-phenotype relationship. Gitelman syndrome was diagnosed based on medical history, clinical manifestations, laboratory test results, and imaging data. The causative gene for Gitelman syndrome, SLC12A3, and the causative gene for the classic Bartter syndrome, CLCNKB, were screened for disease-causing mutations by direct sequencing. Clinical diagnoses of ten patients were consistent with Gitelman syndrome. Disease-causing mutations in the SLC12A3 gene were found in six patients. Among the variants, T60M in exon 1 was the hot spot in Chinese patients. Additionally, we found a small deletion of ACGG in exon 3 and L671P in exon 16; these have not been reported in previous studies. No disease-causing mutations were observed in the other four patients. Since mutations in the SLC12A3 and CLCNKB genes are not present in all patients with clinical manifestations of Gitelman syndrome, genetic screening after clinical diagnosis is essential.

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“…SLC12A3 gene had been identified and speculated that, its genetic variants and rare mutations will impact the development of hypertension, although more mutations are need to verify [ 27 ]. Within Mongolian population, two previous reports also demonstrated the close relationship between SLC12A3 and hypertension, both with random case-control sample and pedigree cohort [ 10 , 11 ]. In this study, within parental group which looked as a rough random population, the subjects with homozygous risk alleles also show a higher blood pressure (Additional file 1 : Table S3).…”

Section: Discussionmentioning

confidence: 81%

“…Asselbergs et al, [ 9 ] confirms the association between SLC12A3 variants and individuals’ HDL-C levels, which may lead to CVD, in a large-scale meta-analysis related to 66,240 individuals of European ancestry. Our previous work also demonstrated a close association between SLC12A3 polymorphism and human hypertension in Mongolians, both within random and pedigree populations [ 10 , 11 ]. Therefore, we hypothesized that SLC12A3 gene might influence individuals’ serum lipid levels, modify their blood pressure, and increase the risk of CVD or related diseases in Mongolians and the aim of this study is to certify the relationship between genetic variants of SLC12A3 and individual’s serum lipid levels in Mongolians.…”

Section: Introductionmentioning

confidence: 73%

Genetic variants of SLC12A3 modulate serum lipid profiles in a group of Mongolian pedigree population

Liang

Zhang

et al. 2018

Lipids Health Dis

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BackgroundThe serum lipid profile, including LDL-C level, is associated with hypertension which is the major cause of cerebrovascular disease (CVD) amounting 30% of global death rate. Previous work also demonstrated important roles of genetic variants of SLC12A3 gene on human CVD, hypertension and other diseases in Mongolian population. However, the relationship between SLC12A3 gene polymorphisms on individuals’ lipid profile is still unknown.MethodsA panel of 15 SNPs of SLC12A3 gene was genotyped within a 424 Mongolians pedigree cohort. The associations between SLC12A3 polymorphisms and four lipid profiles were analyzed by family-based association test (FBAT) and confirmed with haplotype analysis.ResultsFrom both single site and haplotype analyses, the results demonstrated a close relationship between SLC12A3 polymorphisms and LDL-C level. Two SNPs, rs5803 and rs711746 showed significant associations with individuals’ serum LDL-C level (z = − 2.08, P-e = 0.038; z = 2.09, P-e = 0.023, respectively), and distribution of haplotypes constructed by two SNPs also associated with participants’ serum LDL-C level, significantly (Global Chi2 = 9.06 df = 3, P = 0.028).ConclusionOur results demonstrated the importance of SLC12A3 polymorphisms in individuals’ difference about their serum lipid profiles, thereby providing evidence that the genetic variants may contribute to CVD development via modulating person’s LDL-C level and blood pressure, in certain contexts.Electronic supplementary materialThe online version of this article (10.1186/s12944-018-0737-1) contains supplementary material, which is available to authorized users.

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Association of variants in renal salt reabsorption-related gene SLC12A3 with essential hypertension in a Mongolian population

Cited by 3 publications

References 21 publications

SLC12A3 variants modulate LDL cholesterol levels in the Mongolian population

SLC12A3 variants modulate LDL cholesterol levels in the Mongolian population

Clinical and genetic analyses of Chinese patients with Gitelman syndrome

Genetic variants of SLC12A3 modulate serum lipid profiles in a group of Mongolian pedigree population

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