scholarly journals A study of new molecular genetic markers of sudden cardiac death identified in the analysis of the results of whole-exome sequencing

Author(s):  
А.А. Иванова ◽  
Е.С. Мельникова ◽  
А.А. Гуражева ◽  
С.К. Малютина ◽  
В.П. Новоселов ◽  
...  

Целью исследования является подтверждение ассоциации с внезапной сердечной смертью однонуклеотидных полиморфизмов rs77270326, rs34643859, выявленных в ходе собственного полноэкзомного секвенирования как возможных молекулярно-генетических маркеров внезапной сердечной смерти. В группе внезапной сердечной смерти (n=400, средний возраст умерших 53,2±8,7 года, доля мужчин - 70,9%, женщин - 29,1%) и контрольной группе (n=400, средний возраст 53,1±8,3 года, мужчины - 68,3 %, женщины - 31,7%) проведено генотипирование по выбранным полиморфизмам методом ПЦР-ПДРФ по авторским протоколам. По частотам генотипов и аллелей полиморфизма rs77270326 не найдено статистически значимых различий между группами (p>0,05). В группе женщин в возрасте до 50 лет выявлено статистически значимое уменьшение доли носительниц генотипа ТТ в группе внезапной сердечной смерти (32,3%) по сравнению с контрольной группой (60,0%) (ОШ=0,32, 95%ДИ 0,11-0,91, р=0,04). Таким образом, однонуклеотидный полиморфизм rs77270326 не ассоциирован с внезапной сердечной смертью. Для женщин младше 50 лет генотип ТТ полиморфизма rs34643859 ассоциирован с протективным эффектом в отношении внезапной сердечной смерти. The aim of the study is to confirm the association with sudden cardiac death of single-nucleotide polymorphisms rs77270326, rs34643859, identified during own whole-exome sequencing as possible molecular genetic markers of sudden cardiac death. In the group of sudden cardiac death (n = 400, the average age of the dead - 53.2 ± 8.7 years, the proportion of men - 70.9%, women - 29.1%) and the control group (n = 400, average age - 53 , 1 ± 8.3 years, men - 68.3%, women - 31.7%) genotyping of the selected polymorphisms was conducted by PCR-RFLP method according to the authors’ protocols. According to the frequencies of genotypes and alleles of rs77270326 polymorphism, no statistically significant differences were found between the groups (p>0.05). A group of women under the age of 50 revealed a statistically significant decrease in the proportion of carriers of the TT genotype in the group of sudden cardiac death (32.3%) compared with the control group (60.0%) (OR = 0.32, 95% CI 0, 11-0.91, p = 0.04). Thus, the rs77270326 is not associated with sudden cardiac death. For women under the age of 50, the TT genotype of rs34643859 polymorphism is associated with a protective effect against sudden cardiac death.

2020 ◽  
Vol 4 (4) ◽  
pp. 257-267
Author(s):  
Yafei Zhai ◽  
Jinxin Miao ◽  
Ying Peng ◽  
Guangming Fang ◽  
Chuchu Wang ◽  
...  

Long QT syndrome (LQTS), which is caused by an ion channel‐related gene mutation, is a malignant heart disease with a clinical course of a high incidence of ventricular fibrillation and sudden cardiac death in the young. Mutations in KCNH2 (which encodes potassium voltage-gated channel subfamily H member 2) are responsible for LQTS in many patients. Here we report the novel mutation c.1898A>C in KCNH2 in a Chinese family with LQTS through whole-exome sequencing. The c.916dupA mutation in JUP (which encodes junction plakoglobin) is also discovered. Mutations in JUP were found to be associated with arrhythmogenic right ventricular cardiomyopathy. The double mutation in the proband may help explain his severe clinical manifestations, such as sudden cardiac death at an early age. Sequencing for the proband’s family members revealed that the KCNH2 mutation descends from his paternal line, while the mutation in JUP came from his maternal line. The data provided in this study may help expand the spectrum of LQTS-related KCNH2 mutations and add support to the genetic diagnosis and counseling of families affected by malignant arrhythmias.


2021 ◽  
Vol 17 (1) ◽  
pp. 7-11
Author(s):  
A. A. Ivanova ◽  
S. K. Malyutina ◽  
V. P. Novoselov ◽  
I. A. Rodina ◽  
O. V. Khamovich ◽  
...  

The aim of the research is to verify the association with sudden cardiac death (SCD) of single nucleotide polymorphisms rs10867772 and rs4700290, identified as new molecular genetic markers of SCD in the own genome-wide pooled allelotyping.Material and methods. Case-control study. The SCD group is formed using the criteria of the European Society of Cardiology from the DNA bank of suddenly deceased residents of the Oktyabrsky district of Novosibirsk (n = 437, average age—53.1 ± 9.0 years, men — 73.5%, women — 26.5%) The control group (n = 405, average age 53.2 ± 9.2 years, men — 70.0%, women — 30.0%) is formed from the DNA bank of participants of MONICA and HAPIEE projects. DNA was isolated by phenol-­chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by the PCR-RFLP method.Results. No statistical significance was found in allele and genotype frequencies of rs10867772 and rs4700290 between groups, even in separating in sex and age (p> 0.05). Conclusion. Single nucleotide polymorphism rs10867772 and rs4700290 are not associated with SCD.


Author(s):  
A. A. Ivanova ◽  
V. N. Maksimov ◽  
S. K. Malutina ◽  
V. P. Novoselov ◽  
M. I. Voevoda

Aim. To confirm the association between sudden cardiac death (SCD) and single nucleotide polymorphisms rs7164665, rs71461059, rs74765750, rs6762529, identified in own genome-wide associative study as new molecular genetic markers of SCD.Material and methods. As design we used case-control study. The SCD group was formed using the SCD criteria of the European Society of Cardiology (n=438, average age 53,2±9,1 years, male — 72,7%, women — 28,3%). The control group (n=435, average age 53,2±8,9 years, men — 70,0%, women — 30,0%) was selected by gender and age for the SCD group from the DNA bank of the international projects MONICA and HAPIEE. DNA was isolated by phenol-chloroform extraction from myocardial tissue in the SCD group and venous blood in the control group. Genotyping was performed by polymerase chain reaction followed by analysis of estriction fragment length polymorphism. The results are statistically processed using the SPSS 16.0 software package.Results. No carriers of the rare allele A of the single nucleotide polymorphism rs74765750 were found in the SCD group and the control group. No statistically significant differences were found between the SCD group and the control group relating to frequencies of genotypes and alleles of single nucleotide polymorphisms rs7164665 and rs71461059. In the age group older than 50 years, the proportion of carriers of the heterozygous CT genotype of the single nucleotide polymorphism rs6762529 in the SCD group is statistically significantly lower compared to the control group (CT vs CC+TT: OR=0,686, 95% CI 0,483-0,967 p=0,035).Conclusion. The CT genotype of the single nucleotide polymorphism rs6762529 is associated with a protective effect on SCD for people over 50 years of age. The association with single nucleotide polymorphisms rs7164665, rs71461059, rs74765750 with SCD has not been confirmed.


2020 ◽  
Author(s):  
Donglin Zhu ◽  
Minghong Shen ◽  
Jinghuan Lv

Abstract Background: To understand the molecular mechanism of synchronous multifocal lung cancer (SMLC) is of great significance for the differential diagnosis of intrapulmonary metastasis (IM) and synchronous multiple primary lung cancer (SMPLC). Recently, next-generation sequencing (NGS) has become a useful tool for understanding SMLC. Case presentation: In this study, two lesions of a 61-year-old man with lung cancer were detected by whole exome sequencing (WES) and the correlation between different lesions was analyzed at the molecular level. Lesion 1 was adenocarcinoma and lesion 2 was squamous cell carcinoma. Gene mutation and copy number variation (CNV) are different in the two lesions. The genome of lesion 2 is more unstable. The clonal evolution analysis showed that there was no obvious evolutionary relationship between the two lesions, and both lesions were independent double primary lesions. Bioinformatics analysis revealed that the alternate genes of the two lesions were inconsistent in function and pathway. PCA analysis was performed using the Cancer Genome Atlas (TCGA) database and the GTEx database, and it was found that the changed genes in these two lesions were significantly separated from the control group, and the changes of TP53 and EGFR genes in the TCGA database were further described. Conclusions: These results indicate that NGS may provide new ideas for SMLC classification.


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