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01 August 2009

Relationship between haplotypes of KCNN4 gene and susceptibility to human vascular diseases in Japanese

Mai YamaguchiACDEFG, Tomohiro NakayamaABCDEFG, Zhenyan FuCD, Takahiro NaganumaCD, Naoyuki SatoCD, Masayoshi SomaBG, Nobutaka DobaB, Shigeaki HinoharaB, Akihiko MoritaCDEF, Tomohiko MizutaniAG

Med Sci Monit 2009; 15(8): CR389-397 :: ID: 878136

Abstract

Background
Human vascular diseases such as myocardial infarction (MI) and cerebral infarction (CI) are thought to be affected by several environmental factors and genetic variants. It has been suggested that the expression of the KCNN4 calcium-activated potassium channel is associated with the developing vascular smooth-muscle cells of human neointimal hyperplasia. The aim of this study was to investigate the relationship between single-nucleotide polymorphisms (SNPs) in the human KCNN4 gene or haplotypes and the incidence of MI or CI in Japanese.
Material and Method
Three hundred thirteen MI and 176 CI patients with 290 controls were enrolled in two independent case-control studies that examined the use of a haplotype-based case-control study involving five SNPs of the human KCNN4 gene (rs670950, rs2306801, rs2306799, rs347519, and rs3786954).
Results
There were significant differences between the MI and control groups in the overall distribution of genotypes and dominant or recessive models of rs670950, rs2306799, and rs3786954. Multiple logistic regression analyses revealed that even after adjusting for confounding factors (odds ratio: 1.96), the frequency of the G/G genotype of rs2306799 in the MI group was significantly higher than in the control group (p=0.005). Furthermore, the G-T-A haplotype of rs2306799-rs347519-rs3786954 was significantly more frequent in the MI (88.8%) than in the control group (83.6%).
Conclusions
The specific SNPs and haplotypes in the KCNN4 gene showed significant differences between MI and control patients. These results indicate that these polymorphisms and haplotypes could be genetic markers for MI.

Keywords: Linkage Disequilibrium - genetics, Japan, Intermediate-Conductance Calcium-Activated Potassium Channels - genetics, Haplotypes, Genetic Predisposition to Disease, Confidence Intervals, Cerebral Infarction - genetics, Case-Control Studies, Asian Continental Ancestry Group - genetics, Myocardial Infarction - genetics, Odds Ratio, Polymorphism, Single Nucleotide - genetics

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750