THE STUDY OF ASSOCIATION WITH SUDDEN CARDIAC DEATH OF NEW MOLECULAR-GENETIC MARKERS DETECTED IN OWN FULL GENOME ASSOCIATIVE RESEARCH

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.

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Verification of Single Nucleotide Polymorphisms rs34554140, rs6670279, and rs6874185 as Novel Molecular Genetic Markers of Sudden Cardiac Death

Sovremennye tehnologii v medicine ◽

10.17691/stm2021.13.2.04 ◽

2021 ◽

Vol 13 (2) ◽

pp. 40

Author(s):

A.A. Ivanova ◽

A.A. Gurazheva ◽

E.S. Melnikova ◽

A.M. Nesterets ◽

S.K. Malyutina ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Single Nucleotide Polymorphisms ◽

Genetic Markers ◽

Cardiac Death ◽

Molecular Genetic ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Molecular Genetic Markers

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New approaches to the selection of genetic markers associated with multifactorial phenotypic traits

Vestnik of Russian military medical Academy ◽

10.17816/brmma50074 ◽

2020 ◽

Vol 22 (2) ◽

pp. 204-210

Author(s):

G. G. Kutelev ◽

A. B. Krivoruchko ◽

A. E. Trandina ◽

A. M. Ivanov ◽

D. V. Cherkashin ◽

...

Keyword(s):

Genetic Markers ◽

Functional Significance ◽

Molecular Genetic ◽

Candidate Gene Approach ◽

Phenotypic Traits ◽

Diagnostic Efficiency ◽

Full Genome ◽

Structural Variations ◽

Molecular Genetic Markers ◽

Selection Of

Modern approaches to searching for associations between the studied phenotype and structural variations of the human genome are analyzed. Most complex phenotypic traits, including diseases, do not follow the laws of Mendelian inheritance, but have a multi-factor nature, that is, a significant contribution to their development is made by the genetic component in combination with the influence of environmental factors. In General, there are several approaches to the design of a limited set of polymorphic markers for point genotyping. Selection of individual molecular genetic markers is carried out based on either their statistically significant Association with the studied multivariate feature, or their functional significance for the implementation of this feature. The candidate gene approach allows you to focus on one or more polymorphic variants in the region of a gene (allelic variant), the product of which is likely involved in the development of a disease or trait. The cheaper procedure for full-genome screening using ultra-high-density microchips has made available another approach for searching for genetic predispositions - full - genome Association search. We believe that the unification of both approaches into a single algorithm for the choice of molecular genetic markers to conduct point genotyping will allow for both markers selected based on a priori assumptions about the functional significance of candidate genes, and Association with the studied trait on the basis of genome-wide associations search. This approach will optimize the diagnostic efficiency of the created test suite.

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Molecular genetic markers for thyroid FNAB

Nuklearmedizin ◽

10.1055/s-0037-1616610 ◽

2015 ◽

Vol 54 (03) ◽

pp. 94-100 ◽

Cited By ~ 4

Author(s):

P. B. Musholt ◽

T. J. Musholt

Keyword(s):

Genetic Markers ◽

Thyroid Nodules ◽

Molecular Genetic ◽

Genetic Alterations ◽

Diagnostic Tools ◽

Ultrasound Screening ◽

Thyroid Malignancy ◽

Thyroid Carcinomas ◽

Molecular Genetic Markers ◽

The Impact

SummaryAim: Thyroid nodules > 1 cm are observed in about 12% of unselected adult employees aged 18–65 years screened by ultrasound scan (40). While intensive ultrasound screening leads to early detection of thyroid diseases, the determination of benign or malignant behaviour remains uncertain and may trigger anxieties in many patients and their physicians. A considerable number of thyroid resections are consecutively performed due to suspicion of malignancy in the detected nodes. Fine needle aspiration biopsy (FNAB) has been recommended for the assessment of thyroid nodules to facilitate detection of thyroid carcinomas but also to rule out malignancy and thereby avoid unnecessary thyroid resections. However, cytology results are dependent on experience of the respective cytologist and unfortunately inconclusive in many cases. Methods: Molecular genetic markers are already used nowadays to enhance sensitivity and specificity of FNAB cytology in some centers in Germany. The most clinically relevant molecular genetic markers as pre-operative diagnostic tools and the clinical implications for the intraoperative and postoperative management were reviewed. Results: Molecular genetic markers predominantly focus on the preoperative detection of thyroid malignancies rather than the exclusion of thyroid carcinomas. While some centers routinely assess FNABs, other centers concentrate on FNABs with cytology results of follicular neoplasia or suspicion of thyroid carcinoma. Predominantly mutations of BRAF, RET/PTC, RAS, and PAX8/PPARγ or expression of miRNAs are analyzed. However, only the detection of BRAF mutations predicts the presence of (papillary) thyroid malignancy with almost 98% probability, indicating necessity of oncologic thyroid resections irrespective of the cytology result. Other genetic alterations are associated with thyroid malignancy with varying frequency and achieve less impact on the clinical management. Conclusion: Molecular genetic analysis of FNABs is increasingly performed in Germany. Standardization, quality controls, and validation of various methods need to be implemented in the near future to be able to compare the results. With increasing knowledge about the impact of genetic alterations on the prognosis of thyroid carcinomas, recommendations have to be defined that may lead to individually optimized treatment strategies.

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