Dataset Information

Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients.

ABSTRACT: AIM: To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients. METHODS: One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing. RESULTS: Four common A190A, E23K, I337V and 3'UTR +62 G/A polymorphisms were found in KCNJ11. The E23K, I337V and 3'UTR +62 G/A polymorphisms were in complete linkage disequilibrium, and I337V was used as a representative. There were no significant differences in age, body mass index, sex, baseline systolic BP (SBP) and diastolic BP (DBP) among the 3 genotypes for the four polymorphisms. Significant association was found between SBP response and the polymorphisms (adjusted regression coefficient: 3.5 [1.2] mmHg; P=0.003 for the A190A polymorphism; adjusted regression coefficient: 3.1 [1.2] mmHg; P=0.012 for the I337V polymorphism). The patients with TT genotype for A190A polymorphism had higher clinical efficacy than those with CC genotype. CONCLUSION: The results suggest the KCNJ11 polymorphisms are associated with the SBP-lowering response of short-term iptakalim therapy in Chinese Han hypertensive patients.

SUBMITTER: Duan RF

PROVIDER: S-EPMC4002535 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients.

Duan Rui-feng RF Cui Wen-yu WY Wang Hai H

Acta pharmacologica Sinica 20110718 8

<h4>Aim</h4>To study the relationship between the antihypertensive response of iptakalim and KCNJ11 polymorphisms in Chinese Han hypertensive patients.<h4>Methods</h4>One hundred sixty two Chinese Han hypertensive patients were administered iptakalim (5 or 10 mg/d, po) for 8 weeks. Before the treatment and 24 h after completing the treatment blood pressure (BP) was measured. Genotyping was performed using direct sequencing.<h4>Results</h4>Four common A190A, E23K, I337V and 3'UTR +62 G/A polymorp ...[more]

PMID: 21765448

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Project description:BackgroundAntihypertensive therapy is crucial for preventing stroke in hypertensive patients. However, the efficacy of antihypertensive therapy varies across individuals, partially due to therapy-related genetic variations among individuals. We investigated the association of antihypertensive drug-related gene polymorphism with stroke in patients with hypertension.MethodsDemographic information, medication, and outcome data were obtained from a hypertensive patient management system, and a PCR fluorescence probe technique was used to detect 7 gene polymorphic loci (CYP2D6∗10, ADRB1, CYP2C9∗3, AGTR1, ACE, CYP3A5∗3, and NPPA), and these loci were compared between patients with and without stroke. Logistic regression was performed to analyze the association of these genetic variations with stroke risk in hypertensive patients while controlling for potential factors.ResultsThe prevalence of stroke in the hypertensive population in Changsha County of Hunan Province was 2.75%. The mutation frequencies of ADRB1 (1165G > C), CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), NPPA (2238T > C), and CYP3A5∗3 were 74.43%, 57.23%, 4.26%, 5.71%, 31.62%, 1.17%, and 69.58%, respectively. Univariate analysis revealed that ADRB1 polymorphism was associated with stroke (χ2 = 8.659, P < 0.05), with a higher stroke risk in the CC group than in the GC and GG groups (GC + GG). Multivariate unconditional logistic regression analysis showed that the CC genotype in ADRB1 (vs. the GC + GG genotype) was associated with an increased risk of stroke [odds ratio (OR) = 1.184, P<0.05] in hypertensive patients. No association was observed between CYP2D6∗10, CYP2C9∗3, AGTR1 (1166A > C), ACE (I/D), CYP3A5∗3, and NPPA (2238T > C) polymorphisms and stroke.ConclusionsADRB1 (1165G > C) gene polymorphism is associated with the risk of stroke in Chinese hypertensive patients. The CC genotype is correlated with a higher risk of stroke than the GC + GG genotype.

Project description:BACKGROUND: Ghrelin (GHRL) is a pivotal peptide regulator of food intake, energy balance, and body mass. Weight gain (WG) is a common side effect of the atypical antipsychotics (AAPs) used to treat schizophrenia (SZ). Ghrelin polymorphisms have been associated with pathogenic variations in plasma lipid concentrations, blood pressure, plasma glucose, and body mass index (BMI). However, it is unclear whether GHRL polymorphisms are associated with WG due to AAPs. Furthermore, there is no evidence of an association between GHRL polymorphisms and SZ or the therapeutic response to AAPs. We explored these potential associations by genotyping GHRL alleles in SZ patients and controls. We also examined the relation between these SNPs and changes in metabolic indices during AAP treatment in SZ subgroups distinguished by high or low therapeutic response. METHODS: Four SNPs (Leu72Met, -501A/C, -604 G/A, and -1062 G > C) were genotyped in 634 schizophrenia patients and 606 control subjects. RESULTS: There were no significant differences in allele frequencies, genotype distributions, or the distributions of two SNP haplotypes between SZ patients and healthy controls (P > 0.05). There was also no significant difference in symptom reduction between genotypes after 8 weeks of AAP treatment as measured by positive and negative symptom scale scores (PANSS). However, the -604 G/A polymorphism was associated with a greater BMI increase in response to AAP administration in both APP responders and non-responders as distinguished by PANSS score reduction (P < 0.001). There were also significant differences in WG when the responder group was further subdivided according to the specific AAP prescribed (P < 0.05). CONCLUSIONS: These four GHRL gene SNPs were not associated with SZ in this Chinese Han population. The -604 G/A polymorphism was associated with significant BW and BMI increases during AAP treatment. Patients exhibiting higher WG showed greater improvements in positive and negative symptoms than patients exhibiting lower weight gain or weight loss.

Dataset Information

Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients.

Publications

Association of the antihypertensive response of iptakalim with KCNJ11 (Kir6.2 gene) polymorphisms in Chinese Han hypertensive patients.

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