KCNQ1 Polymorphism and Susceptibility to Sudden Cardiac Death in Chinese Population

Background: SCD (Sudden Cardiac Death) occurs commonly in forensic practice and often shows negative anatomy results after a systemic autopsy. In recent years, the importance of genetic background has been emphasized in the examination of SCD. The aim of this study is to establish a feasible method to detect SCD-related mutations located in a SCD-causing gene, potassium voltage-gated channel gene (KCNQ1). This method will meet the requirement of mutation screening for SCD in regular forensic DNA laboratories.   Methods: 51 reported single nucleotide polymorphisms (SNPs) from KCNQ1 gene were selected in our study. We examined 60 SCD victims and 60 healthy individuals from the Chinese population residing in Shanxi and Chongqing, China. We performed multiplex PCR for 16 DNA fragments, then using SNaPshot reaction and capillary electrophoresis to obtain the typing results of 51 SNPs. Finding: Four previously reported coding variants were identified in our study: S546S, I145I, P448R and G643S. The allele frequencies of I145I did not differ significantly in the SCD cases compared with Chinese controls (I145I: 10% in SCD cases vs 6% in controls, p=0*301, OR=0*965). The heterozygous mutation of G643S and P448R probably were putative causative mutation for SCD in Chinese population (G643S: 40% in SCD cases vs 10% in controls, p<0*0001, OR=4*000; For P448R: 35% in SCD cases vs 8*3% in controls, p<0*001, OR=4*200). S546S was the 4th mutation found in SCD population resulting in 35% in SCD cases and 18*3% in controls (p=0*049, OR=0*883).   Interpretation: The missense mutation of KCNQ1 gene, P448R and G643S, were associated with SCD susceptibility level in Chinese population. The established system would be potentially helpful for investigating the characteristic of SCD-related mutations in KCNQ1 gene. These methods are compatible with current techniques and equipments in forensic DNA laboratory and will help screen mutations in those dead of SCD and their relatives. Funding Statement: This work was supported by the Natural Science Foundation of China (No. 30900593), the Natural Science Foundation of Shanxi Province, China (No. 201601D011091), Scientific Research Foundation for Returned Overseas Chinese Scholars of Shanxi Province (2011-172) and Shanxi Scholarship Council of China (2016-055). Declaration of Interests: The authors have no financial or commercial conflicts of interest. Ethics Approval Statement: The sample collection was approved by the ethics committee of Shanxi Medical University, China. Written informed consent was obtained from participants or their family members, who agreed to use the data for this study.