Contribution of five top whole-genome association signals to hypertension in Han Chinese

Wq, Niu; Zhang, Y; Kd, Ji; Gao, Peng; Zhu, Dingliang

doi:10.1038/jhh.2010.114

Cited by 7 publications

(6 citation statements)

References 10 publications

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“…According to a multi-center observation in China, the average urinary sodium excretion in northern Chinese (271 mmol per day) is nearly double the amount of that in southern Chinese (139 mmol per day), leading to average 7.4 and 6.9 mmHg increases of systolic and diastolic BP, respectively30. In view of the divergent STK39-hypertension association between northeastern (the present study) and southern Chinese16, it seems reasonable to speculate that the high-salt intake may modify an individual's genetic predisposition to hypertension. In fact, STK39 encodes a protein kinase more commonly known as SPAK, which participates in a signaling pathway that activates thiazide-sensitive NaCl cotransport in the kidney.…”

Section: Discussionmentioning

confidence: 53%

“…Unfortunately none of these polymorphisms were successfully replicated for hypertension risk16. Moreover, another replication in a British Caucasian cohort also failed to detect any relationship between these polymorphisms and BP variation19.…”

Section: Discussionmentioning

confidence: 99%

“…These polymorphisms have been reported to be associated with hypertension or BP by many studies57161920. The genomic organization of human STK39 gene and the localization of five examined polymorphisms are provided in Supplementary material online, Figure S1.…”

Section: Methodsmentioning

confidence: 99%

“…The genomic sequence of STK39 gene is polymorphic and so far 34 polymorphisms have been validated by SNPbrowser™. Several genetic polymorphisms in STK39 gene have been reported to be associated with hypertension; however, the results are often not reproducible1213141516. To generate more information and unveil an epistatic picture, we in this study focused on five well-characterized common polymorphisms of STK39 gene, aiming to examine their individual and interactive association with the risk of hypertension among northeastern Han Chinese.…”

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confidence: 99%

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Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese

Zhao

Wang

et al. 2014

Sci Rep

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Serine/threonine kinase 39 (STK39) gene has been reported to be a hypertension-susceptibility gene by a recent genome-wide association study in Western populations. To validate this finding in Chinese, we focused on five well-characterized common polymorphisms in STK39 gene to examine their potential association with hypertension in a large northeastern Han population. This is a hospital-based case-control study involving 1009 hypertensive patients and 756 normotensive controls. Data were analyzed by the Haplo.Stats and multifactor dimensionality reduction (MDR) softwares. The genotype and allele distributions of rs6749447, rs3754777 and rs6433027 differed significantly between patients and controls (P < 0.001) even after the Bonferroni correction. The majority of derived haplotypes also showed remarkable differences between the two groups (P ≤ 0.001). As indicated by MDR analysis, a three-locus model including rs6749447, rs35929607 and rs3754777 was selected as the overall best with a larger testing accuracy of 0.7309 and a maximum cross-validation consistency of 10 (P < 0.001). The utility of this model was reinforced by a Logistic regression analysis. Taken together, our findings suggest the potential interactive role of STK39 gene multiple polymorphisms in the development of hypertension among northeastern Han Chinese.

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Section: Discussionmentioning

confidence: 53%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

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Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese

Zhao

Wang

et al. 2014

Sci Rep

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“…In the two large GWAS, using more than 60000 people, the effects of STK39 SNPs on BP were not found 5)6). In addition, in one British7) and one Chinese8) study, variants of STK39 were not associated with BP. Recently, Rhee et al9) reported four previously reported SNPs associated with salt-sensitivity in 101 Koreans.…”

Section: Discussionmentioning

confidence: 94%

Association betweenSerine/Threonine Kinase 39Gene Polymorphism, Hypertension, and Other Cardiovascular Risk Factors in Koreans

et al. 2013

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Background and ObjectivesAlthough the association between single nucleotide polymorphisms (SNPs) of Serine/Threonine Kinase 39 (STK39) and hypertension has been reported, the prior studies have been inconsistent. The aim of this study is to evaluate the association between rs3754777 and rs6749447, the two SNPs of STK39, and hypertension and other cardiovascular risk factors in Koreans, residing in the Republic of Korea.Subjects and MethodsWe included 238 hypertensive patients and 260 controls. The associations between genotype and haplotype combination and hypertension were examined. In addition, possible SNP-related differences in the adjusted blood pressure and other cardiovascular risk factors were analyzed.ResultsThere was no significant association between the two SNPs and hypertension. However, the carriers of AA genotype of rs3754777 showed lower blood glucose and cholesterol levels, particularly in females. Genotype of rs6749447 was associated with the waist circumference, triglyceride, and high density lipoprotein-cholesterol levels, only in gender-stratified analysis. The effects of haplotype combinations on risk factors were compatible with genotype effects of each SNP.ConclusionAssociations between the two SNPs of STK39, rs3754777 and rs6749447, and hypertension were not significant. However, the two SNPs showed genotype-related differences in blood glucose, lipids, and waist circumference, especially in women. Further studies are needed to clarify the effect of STK39 variants in these cardiovascular risk factors.

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Replication of the top 10 most significant polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians

Zhao

Wang

et al. 2013

Hypertens Res

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The replication of genome-wide significant association signals in independent populations is a practical approach for characterizing gene-disease relationships. Therefore, we sought to explore the top 10 polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians. This was a hospital-based study involving 1009 patients with essential hypertension and 756 normotensive controls from Qiqihar city, China. Genotyping was conducted with a polymerase chain reaction-ligase detection reaction method. All polymorphisms except for rs6825911 satisfied Hardy-Weinberg equilibrium. Overall, the genotype differences between the patients and controls were significant for rs35444 (P<0.001), rs11191548 (P=0.017) and rs17249754 (P=0.017). The per-minor-allele odds ratios of rs35444, rs11191548 and rs17249754 were 0.54 (95% confidence interval (95% CI): 0.46-0.62; P<0.01), 1.23 (95% CI: 1.07-1.43; P=0.005) and 1.23 (95% CI: 1.07-1.41; P=0.004), respectively. Similarly, the carriers of minor homozygotes had a significant reduction in adjusted systolic and diastolic blood pressure for rs35444 (P<0.01) but an increase for both rs11191548 (P<0.01) and rs17249754 (P<0.04). Further application of the genetic risk score method indicated that subjects with risk scores of 8, 10 and 12-16 had 1.66-fold (95% CI: 1.01-2.72), 1.72-fold (95% CI: 1.03-2.86) and 1.97-fold (95% CI: 1.12-3.46) increases, respectively, in the odds of developing hypertension, and similar increases were also observed for blood pressure. Taken together, our findings demonstrate that although only three of the top 10 polymorphisms were successfully validated in the northeastern Han Chinese population, the genetic risk score analyses led us to more profound insights into the possible joint effects of multiple polymorphisms on hypertension risk and blood pressure variation.

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Contribution of five top whole-genome association signals to hypertension in Han Chinese

Cited by 7 publications

References 10 publications

Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese

Interactive contribution of serine/threonine kinase 39 gene multiple polymorphisms to hypertension among northeastern Han Chinese

Association betweenSerine/Threonine Kinase 39Gene Polymorphism, Hypertension, and Other Cardiovascular Risk Factors in Koreans

Replication of the top 10 most significant polymorphisms from a large blood pressure genome-wide association study of northeastern Han Chinese East Asians

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