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

Abstract

ABSTRACT. 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 Renal salt reabsorption-related gene and hypertension mass index, alcohol consumption, total plasma cholesterol, and lowdensity 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, ClCKb-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.

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

“…However, they failed to demonstrate a correlation between the Arg904Gln variant and hypertension in a Canadian population. On the other hand, Wang et al (2008) and our earlier study (Chang et al, 2011a) reported that the Arg904Gln polymorphism of the SLC12A3 gene had no significant association with hypertension in Uyghur, Kazak, and Mongolian populations, which are minority populations in China. Furthermore, a case-control study performed by Aoi et al (2008), following examination of three SLC12A3 mutations including T180K, A569V, and L849H, verified that the SLC12A3 gene was not involved in essential hypertension in a Japanese population.…”

Novel diuretic targets

“…This suggestion is further supported by the observation of an association between a common ClC-Kb polymorphism that increases channel activity and a predisposition to hypertension (7,37,62,73,126). However, it should be noted that such a predisposition has not been detected in all studies (17,37,73,132). It has been suggested that salt-loading conditions as well as sex and ethic segregation need to be considered, and that larger studies are necessary to resolve the issue (73,126,150).…”

Polymorphisms in the <b><i>SLC12A3</i></b> Gene Encoding Sodium-Chloride Cotransporter are Associated with Hypertension: A Family-Based Study in the Mongolian Population

“…Zhang et al [17] have reported the lack of association between Arg904Gln substitution and essential hypertension based on a meta-analysis, while other studies did not observe the relationship of reported SLC12A3 polymorphisms with hypertension in rats [18] and humans [19]. Similarly, the Arg904Gln polymorphism in NCC did not show correlation with hypertension, as evidenced by the investigation of two ethnic groups in Northwest China [20] and our earlier study in the Uyghurs, Kazaks, and Mongolians [21], ethnic minorities in China. However, these and other related studies based on random or specific populations have not performed stratification for genetic admixture which may be a confounding factor affecting the conclusion about the link between SLC12A3 genetic variants and hypertension.…”

“…Patients were in sitting position when blood pressure was measured as described previously [21]: 1) three times with 2-min intervals between the measurements; 2) SBP and DPB were recorded to the nearest 2 mmHg at the appearance of the first (phase I) and disappearance of the fifth (phase V) Korotkoff sounds, respectively; 3) three consecutive measurements were averaged. Body mass index (BMI) was calculated as the body weight in kilograms divided by the square of height in meters.…”

“…In our previous study, we have investigated the relationship between the SLC12A3 gene and hypertension and found that two tag SNPs are predisposing genetic factors for hypertension in the Han population dominant in China [21]. In the current study, we aimed to analyze the association of the common SLC12A3 variants with the occurrence of essential hypertension among the inhabitants of the Inner Mongolia region, which has not been yet established.…”