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      저자 : Michael A Olaopa (검색결과 1 건)
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        Genetic Variation of SCN5A in Korean Patients with Sick Sinus Syndrome

        Young-Soo Lee,Michael A Olaopa,정병천,이상희,신동구,박형섭,조용근,한상미,이명훈,김윤년 대한심장학회 2016 Korean Circulation Journal Vol.46 No.1

        Background and Objectives: Due to recent studies that have shown an association between the genetic variation of SCN5A and sick sinus syndrome (SSS), we sought to determine if a similar correlation existed in Korean patients with SSS. Subjects and Methods: We enrolled 30 patients with SSS who showed a sinus pause (longer than 3.0 s) in Holter monitoring, in addition to 80 controls. All exons including the putative splicing sites of the SCN5A gene were amplified by polymerase chain reaction and sequenced either directly or following subcloning. Wild-type and single nucleotide polymorphisms were expressed in human embryonic kidney cells, and the peak sodium current (INa) was analyzed using the whole-cell patch-clamp technique. Results: A total of 9 genetic variations were identified: 7 variations (G87A-A29A, IVS9-3C>A, A1673G-H558R, G3823A-D1275N, T5457C-D1819D, T5963G-L1988R, and C5129T-S1710L) had been previously reported, and 2 variants (A3075T-E1025D and T4847A-F1616Y) were novel; the potential structural effects of F1616Y were analyzed in a three-dimensional model of the SCN5A domain. Patch-clamp studies at room temperature demonstrated that the peak INa was significantly increased by 140% in HEK cells transfected with F1616Y comparedwith wild-type (-335.13 pA/pF±24.04, n=8 vs. -139.95 pA/pF±23.76, n=7, respectively). Furthermore, the voltage dependency of theactivation and steady-state inactivation of F1616Y were leftward-shifted compared with wild-type (Vh activation=-55.36 mv±0.22, n=8 vs. Vh activation=-44.21 mV±0.17, n=7; respectively; Vh inactivation=-104.47 mV±0.21, n=7 vs. Vh inactivation=-84.89 mV±0.09, n=12, respectively). Conclusion: F1616Y may be associated with SSS.

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