No association of the rs2954029 variant of the TRIB1 gene with blood lipid parameters and myocardial infarction in the Caucasian population of Western Siberia

Cardiovascular diseases (CVD) are currently one of the leading causes of morbidity and disability in the Russian Federation. In addition to lifestyle factors, individual risk of adverse cardiovascular outcomes is determined by genetic factors.

The aim of this study was to investigate the association of the rs2954029 variant of the TRIB1 gene with a number of clinical and biochemical parameters, as well as the risk of myocardial infarction (MI), in the Caucasian population of Western Siberia.

Material and methods. The study included 1,301 participants in the HAPIEE project (57,0±0,2 years; 46.3 % men). Data on new cases of myocardial infarction in the observed cohort were collected based on the Novosibirsk City Registry of Myocardial Infarction. Genotyping of rs2954029 was performed using Real-Time PCR.

Results. The allele frequency in the Caucasian population group of Western Siberia was A = 0.495, T = 0.505 and significantly differs from other European, non-Finnish, populations (p = 0.008). The genotype frequency was AA = 0.24, AT = 0.52, and TT = 0.24. No statistically significant association was found between this variant and lipid profile parameters and MI either in the overall group or in the subgroups of men and women.

Conclusions. In terms of T allele frequency of rs2954029 of the TRIB1 gene, the Caucasian population of Western Siberia occupies an intermediate position between European populations and populations of Central and East Asia. This study revealed no statistically significant association between the rs2954029 variant of the TRIB1 gene and clinical and biochemical parameters, or with the risk of developing myocardial infarction in the Caucasian population of Western Siberia.

1. Russian Statistical Yearbook. 2024: Statistical Collection / Rosstat. Moscow, 2024. 630 p. (In Russ.)

2. Atar D., Jukema J.W., Molemans B., Taub P.R., Shinya S., Mach F., CerezoOlmos C., Underberg J., Keech A., Tokgözoğlu L., Bonaca M.P. New cardiovascular prevention guidelines: How to optimally manage dyslipidaemia and cardiovascular risk in 2021 in patients needing secondary prevention? Atherosclerosis. 2021; 319: 51–61. doi: 10.1016/j.atherosclerosis.2020.12.013

3. Eyers P.A., Keeshan K., Kannan N. Tribbles in the 21st Century: The Evolving Roles of Tribbles Pseudokinases in Biology and Disease. Trends in Cell. Biol. 2017; 27: 284–298. doi: 10.1016/j.tcb.2016.11.002

4. Lohan F., Keeshan K. The functionally diverse roles of tribbles. Biochem. Soc. Trans. 2013; 41: 1096–1100. doi: 10.1074/jbc.M703735200

5. Salazar M., Lorente M., García-Taboada E., Pérez Gómez E., Dávila D., Zúñiga-García P., María Flores J., Rodríguez A., Hegedus Z., Mosén-Ansorena D., Aransay A.M., Hernández-Tiedra S., López-Valero I., Quintanilla M., Sánchez C., Iovanna J.L., Dusetti N., Guzmán M., Francis S.E., Carracedo A., Kiss-Toth E., Velasco G. Loss of Tribbles pseudokinase-3 promotes Aktdriven tumorigenesis via FOXO inactivation. Cell. Death. Differ. 2015; 22: 131–144. doi: 10.1038/cdd.2014.133

6. Hegedus Z., Czibula A., Kiss-Toth E. Tribbles: a family of kinase-like proteins with potent signalling regulatory function. Cell. Signal. 2007; 19: 238–250. doi: 10.1016/j.cellsig.2006.06.010

7. Du K., Herzig S., Kulkarni R.N., Montminy M. TRB3: A tribbles Homolog That Inhibits Akt/PKB Activation by Insulin in Liver. Science. 2003; 300: 1574–1577. doi: 10.1126/science.1079817

8. Zanella F., Renner O., García B., Callejas S., Dopazo A., Peregrina S., Carnero A., Link W. Human TRIB2 is a repressor of FOXO that contributes to the malignant phenotype of melanoma cells. Oncogene. 2010; 29: 2973–2982. doi: 10.1038/onc.2010.58

9. Jadhav K.S., Bauer R.C. Trouble With Tribbles-1. Arterioscler. Thromb. Vasc. Biol. 2019; 39 (6): 998–1005. doi: 10.1161/ATVBAHA.118.311573

10. Kathiresan S., Melander O., Guiducci C., Surti A., Burtt N.P., Rieder M.J., Cooper G.M., Roos C., Voight B.F., Havulinna A.S., Wahlstrand B., Hedner T., Corella D., Tai E.S., Ordovas J.M., Berglund G., Vartiainen E., Jousilahti P., Hedblad B., Taskinen M.-R., Newton-Cheh C., Salomaa V., Peltonen L., Groop L., Altshuler D.M., Orho-Melander M. Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol ortriglycerides in humans. Nat. Genet. 2008; 40 (2): 189– 97. doi: 10.1038/ng.75

11. Willer C.J., Sanna S., Jackson A.U., Scuteri A., Bonnycastle L.L., Clarke R., Heath S.C., Timpson N.J., Najjar S.S., Stringham H.M., Strait J., Duren W.L., Maschio A., Busonero F., Mulas A., Albai G., Swift A.J., Morken M.A., Narisu N., Bennett D., Parish S., Shen H., Galan P., Meneton P., Hercberg S., Zelenika D., Chen W.-M., Li Y., Scott L.J., Scheet P.A., Sundvall J., Watanabe R.M., Nagaraja R., Ebrahim S., Lawlor D.A., Ben-Shlomo Y., Davey-Smith G., Shuldiner A.R., Collins R., Bergman R.N., Uda M., Tuomilehto J., Cao A., Collins F.C., Lakatta E., Lathrop G.M., Boehnke M., Schlessinger D., Mohlke K.L., Abecasis G.R. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat. Genet. 2008; 40 (2): 161–169. doi: 10.1038/ng.76

12. Teslovich T.M., Musunuru K., Smith A.V., Edmondson A.C., Stylianou I.M., Koseki M., Pirruccello J.P., Ripatti S., Chasman D.I., Willer C.J., Johansen C.T., Fouchier S.W., Isaacs A., Peloso G.M., Barbalic M., Ricketts S.L., Bis J.C., Aulchenko Y.S., Thorleifsson G., Feitosa M.F., Chambers J., Orho-Melander M., Melander O., Johnson T., Li X., Guo X., Li M., Shin Cho Y., Jin Go M., Jin Kim Y., Lee J.Y., Park T., Kim K., Sim X., Twee-Hee Ong R., Croteau-Chonka D.C., Lange L.A., Smith J.D., Song K., Hua Zhao J., Yuan X., Luan J., Lamina C., Ziegler A., Zhang W., Zee R.Y., Wright A.F., Witteman J.C., Wilson J.F., Willemsen G., Wichmann H.E., Whitfield J.B., Waterworth D.M., Wareham N.J., Waeber G., Vollenweider P., Voight B.F., Vitart V., Uitterlinden A.G., Uda M., Tuomilehto J., Thompson J.R., Tanaka T., Surakka I., Stringham H.M., Spector T.D., Soranzo N., Smit J.H., Sinisalo J., Silander K., Sijbrands E.J., Scuteri A., Scott J., Schlessinger D., Sanna S., Salomaa V., Saharinen J., Sabatti C., Ruokonen A., Rudan I., Rose L.M., Roberts R., Rieder M., Psaty B.M., Pramstaller P.P., Pichler I., Perola M., Penninx B.W., Pedersen N.L., Pattaro C., Parker A.N., Pare G., Oostra B.A., O’Donnell C.J., Nieminen M.S., Nickerson D.A., Montgomery G.W., Meitinger T., McPherson R., McCarthy M.I., McArdle W., Masson D., Martin N.G., Marroni F., Mangino M., Magnusson P.K.E., Lucas G., Luben R., Loos R.J.F., Lokki M.-L., Lettre G., Langenberg C., Launer L.J., Lakatta E.G., Laaksonen R., Kyvik K.O., Kronenberg F., König I.R., Khaw K.-T., Kaprio J., Kaplan L.M., Johansson A., Jarvelin M.-R., A Janssens C.J.W., Ingelsson E., Igl W., Hovingh G.K., Hottenga J.-J., Hofman A., Hicks A.A., Hengstenberg C., Heid I.M., Hayward C., Havulinna A.S., Hastie N.D., Harris T.B., Haritunians T., Hall A.S., Gyllensten U., Guiducci C., Groop L.C., Gonzalez E., Gieger C., Freimer N.B., Ferrucci L., Erdmann J., Elliott P., Ejebe K.G., Döring A., Dominiczak A.F., Demissie S., Deloukas P., de Geus E.J.C., de Faire U., Crawford G., Collins F.S., Chen Y.I., Caulfield M.J., Campbell H., Burtt N.P., Bonnycastle L.L., Boomsma D.I., Boekholdt S.M., Bergman R.N., Barroso I., Bandinelli S., Ballantyne C.M., Assimes T.L., Quertermous T., Altshuler D., Seielstad M., Wong T.Y., TaiE.-S., Feranil A.B., Kuzawa C.W., Adair L.S., Taylor H.A. Jr., Borecki I.B., Gabriel S.B., Wilson J.G., Holm H., Thorsteinsdottir U., Gudnason V., Krauss R.M., Mohlke K.L., Ordovas J.M., Munroe P.B., Kooner J.S., Tall A.R., Hegele R.A., Kastelein J.J.P., Schadt E.E., Rotter J.I., Boerwinkle E., Strachan D.P., Mooser V., Stefansson K., Reilly M.P., Samani N.J., Schunkert H., Cupples L.A., Sandhu M.S., Ridker P.M., Rader D.J., van Duijn C.M., Peltonen L., Abecasis G.R., Boehnke M., Kathiresan S. Biological, clinical and population relevance of 95 loci for blood lipids. Nature. 2010; 466: 707–713. doi: 10.1038/nature09270

13. Willer C.J., Schmidt E.M., Sengupta S., Peloso G.M., Gustafsson S., Kanoni S., Ganna A., Chen J., Buchkovich M.L., Mora S., Beckmann J.S., Bragg-Gresham J.L., Chang H.Y., Demirkan A., Den Hertog H.M., Do R., Donnelly L.A., Ehret G.B., Esko T., Feitosa M.F., Ferreira T., Fischer K., Fontanillas P., Fraser R.M., Freitag D.F., Gurdasani D., Heikkilä K., Hyppönen E., Isaacs A., Jackson A.U., Johansson Å., Johnson T., Kaakinen M., Kettunen J., Kleber M.E., Li X., Luan J., Lyytikäinen L.P., Magnusson P.K.E., Mangino M., Mihailov E., Montasser M.E., Müller-Nurasyid M., Nolte I.M., O’Connell J.R., Palmer C.D., Perola M., Petersen A.K., Sanna S., Saxena R., Service S.K., Shah S., Shungin D., Sidore C., Song C., Strawbridge R.J., Surakka I., Tanaka T., Teslovich T.M., Thorleifsson G., van den Herik E.G., Voight B.F., Volcik K.A., Waite L.L., Wong A., Wu Y., Zhang W., Absher D., Asiki G., Barroso I., Been L.F., Bolton J.L., Bonnycastle L.L., Brambilla P., Burnett M.S., Cesana G., Dimitriou M., Doney A.S.F., Döring A., Elliott P., Epstein S.E., Ingi Eyjolfsson G., Gigante B., Goodarzi M.O., Grallert H., Gravito M.L., Groves C.J., Hallmans G., Hartikainen A.L., Hayward C., Hernandez D., Hicks A.A., Holm H., Hung Y.J., Illig T., Jones M.R., Kaleebu P., Kastelein J.J.P., Khaw K.T., Kim E., Klopp N., Komulainen P., Kumari M., Langenberg C., Lehtimäki T., Lin S.-Y., Lindström J., Loos R.J.F., Mach F., McArdle W.L., Meisinger C., Mitchell B.D., Müller G., Nagaraja R., Narisu N., Nieminen T.V.M., Nsubuga R.N., Olafsson I., Ong K.K., Palotie A., Papamarkou T., Pomilla C., Pouta A., Rader D.J., Reilly M.P., Ridker P.M., Rivadeneira F., Rudan I., Ruokonen A., Samani N., Scharnagl H., Seeley J., Silander K., StančákováA., Stirrups K., Swift A.J., Tiret L., Uitterlinden A.G., van Pelt L.J., Vedantam S., Wainwright N., Wijmenga C., Wild S.H., Willemsen G., Wilsgaard T., Wilson J.F., Young E.H., Zhao J.H., Adair L.S., Arveiler D., Assimes T.L., Bandinelli S., Bennett F., Bochud F., Boehm B.O., Boomsma D.I., Borecki I.B., Bornstein S.R., Bovet P., Burnier M., Campbell H., Chakravarti A., Chambers J.C., Chen Y.-D.I., Collins F.S., Cooper R.S., Danesh J., Dedoussis G., de Faire U., Feranil A.B., Ferrières J., Ferrucci L., Freimer N.B., Gieger C., Groop L.C., Gudnason V., Gyllensten U., Hamsten A., Harris T.B., Hingorani A., Hirschhorn J.N., Hofman A., Hovingh G.K., Hsiung C.A., Humphries S.E., Hunt S.C., Hveem K., Iribarren C., Järvelin M.-R., Jula A., Kähönen M., Kaprio J., Kesäniemi A., Kivimaki M., Kooner J.S., Koudstaal P.J., Krauss R.M., Kuh D., Kuusisto J., Kyvik K.O., Laakso M., Lakka T.A., Lind L., Lindgren C.M., Martin N.G., März W., McCarthy M.I., McKenzie C.A., Meneton P., Metspalu A., Moilanen L., Morris A.D., Munroe P.B., Njølstad I., Pedersen N.L., Power C., Pramstaller P.P., Price J.F., Psaty B.M., Quertermous T., Rauramaa R., Saleheen D., Salomaa V., Sanghera D.K., Saramies J., Schwarz P.E.H., Sheu W.H.-H., Shuldiner A.R., Siegbahn A., Spector T.D., Stefansson K., Strachan D.P., Tayo B.O., Tremoli E., Tuomilehto J., Uusitupa M., van Duijn C.M., Vollenweider P., Wallentin L., Wareham N.J., Whitfield J.B., Wolffenbuttel B.H.R., Ordovas J.M., Boerwinkle E., Palmer C.N.A., Thorsteinsdottir U., Chasman D.I., Rotter J.I., Franks P.W., Ripatti S., Cupples L.A., Sandhu M.S., Rich S.S., Boehnke M., Deloukas P., Kathiresan S., Mohlke K.L., Ingelsson E., Abecasis G.R.; Global Lipids Genetics Consortium. Discovery and refinement of loci associated with lipid levels. Nat. Genet. 2013; 45: 1274– 1283. doi: 10.1038/ng.2797

14. Klarin D., Damrauer S.M., Cho K., Sun Y.V., Teslovich T.M., Honerlaw J., Gagnon D.R., DuVall S.L., Li J., Peloso G.M., Chaffin M., Small A.M., Huang J., Tang H., Lynch J.A., Ho Y.L., Liu D.J., Emdin C.A., Li A.H., Huffman J.E., Lee J.S., Natarajan P., Chowdhury R., Saleheen D., Vujkovic M., Baras A., Pyarajan S., Di Angelantonio E., Neale B.M., Naheed A., Khera A.V., Danesh J., Chang K.M., Abecasis G., Willer C., Dewey F.E., Carey D.J.; Global Lipids Genetics Consortium; Myocardial Infarction Genetics (MIGen) Consortium; Geisinger-Regeneron DiscovEHR Collaboration; VA Million Veteran Program; Concato J., Gaziano J.M., O’Donnell C.J., Tsao P.S., Kathiresan S., Rader D.J., Wilson P.W.F., Assimes T.L. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program. Nat. Genet. 2018; 50: 1–14. doi: 10.1038/s41588-018-0222-9

15. CARDIoGRAMplusC4D Consortium, Deloukas P., Kanoni S., Willenborg C., Farrall M., Assimes T.L., Thompson J.R., Ingelsson E., Saleheen D., Erdmann J., Goldstein B.A., Stirrups K., König I.R., Cazier J.B., Johansson A., Hall A.S., Lee J.Y., Willer C.J., Chambers J.C., Esko T., Folkersen L., Goel A., Grundberg E., Havulinna A.S., Ho W.K., Hopewell J.C., Eriksson N., Kleber M.E., Kristiansson K., Lundmark P., Lyytikäinen L.P., Rafelt S., Shungin D., Strawbridge R.J., Thorleifsson G., Tikkanen E., Van Zuydam N., Voight B.F., Waite L.L., Zhang W., Ziegler A., Absher D., Altshuler D., Balmforth A.J., Barroso I., Braund P.S., Burgdorf C., Claudi-Boehm S., Cox D., Dimitriou M., Do R.; DIAGRAM Consortium, CARDIOGENICS Consortium, Doney A.S., El Mokhtari N., Eriksson P., Fischer K., Fontanillas P., Franco-Cereceda A., Gigante B., Groop L., Gustafsson S., Hager J., Hallmans G., Han B.G., Hunt S.E., Kang H.M., Illig T., Kessler T., Knowles J.W., Kolovou G., Kuusisto J., Langenberg C., Langford C., Leander K., Lokki M.L., Lundmark A., McCarthy M.I., Meisinger C., Melander O., Mihailov E., Maouche S., Morris A.D., Müller-Nurasyid M.; MuTHER Consortiumm, Nikus K., Peden J.F., Rayner N.W., Rasheed A., Rosinger S., Rubin D., Rumpf M.P., Schäfer A., Sivananthan M., Song C., Stewart A.F., Tan S.T., Thorgeirsson G., van der Schoot C.E., Wagner P.J., Wellcome Trust Case Control Consortium, Wells G.A., Wild P.S., Yang T.-P., Amouyel P., Arveiler D., Basart H., Boehnke M., Boerwinkle E., Brambilla P., Cambien F., Cupples A.L., de Faire U., Dehghan A., Diemert P., Epstein S.E., Evans A., Ferrario M.M., Ferrières J., Gauguier D., Go A.S., Goodall A.H., Gudnason V., Hazen S.L., Holm H., Iribarren C., Jang Y., Kähönen M., Kee F., Kim H.-S., Klopp N., Koenig W., Kratzer W., Kuulasmaa K., Laakso M., Laaksonen R., Lee J.-Y., Lind L., Ouwehand W.H., Parish S., Park J.E., Pedersen N.L., Peters A., Quertermous T., Rader D.J., Salomaa V., Schadt E., Shah S.H., Sinisalo J., Stark K., Stefansson K., Trégouët D.-A., Virtamo J., Wallentin L., Wareham N., Zimmermann M.E., Nieminen M.S., Hengstenberg C., Sandhu M.S., Pastinen T., Syvänen A.-C., Hovingh G.K., Dedoussis G., Franks P.W., Lehtimäki T., Metspalu A., Zalloua P.A., Siegbahn A., Schreiber S., Ripatti S., Blankenberg S.S., Perola M., Clarke R., Boehm B.O., O’Donnell C., Reilly M.P., März W., Collins R., Kathiresan S., Hamsten A., Kooner J.S., Thorsteinsdottir U., Danesh J., Palmer C.N.A., Roberts R., Watkins H., Schunkert H., Samani N.J. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat. Genet. 2013; 45: 25–33. doi: 10.1038/ng.2480

16. Nikpay M., Goel A., Won H.H., Hall L.M., Willenborg C., Kanoni S., Saleheen D., Kyriakou T., Nelson C.P., Hopewell J.C., Webb T.R., Zeng L., Dehghan A., Alver M., Armasu S.M., Auro K., Bjonnes A., Chasman D.I., Chen S., Ford I., Franceschini N., Gieger C., Grace C., Gustafsson S., Huang J., Hwang S.J., Kim Y.K., Kleber M.E., Lau K.W., Lu X., Lu Y., Lyytikäinen L.P., Mihailov E., Morrison A.C., Pervjakova N., Qu L., Rose L.M., Salfati E., Saxena R., Scholz M., Smith A.V., Tikkanen E., Uitterlinden A., Yang X., Zhang W., Zhao W., de Andrade M., de Vries P.S., van Zuydam N.R., Anand S.S., Bertram L., Beutner F., Dedoussis G., Frossard P., Gauguier D., Goodall A.H., Gottesman O., Haber M., Han B.G., Huang J., Jalilzadeh S., Kessler T., König I.R., Lannfelt L., Lieb W., Lind L., Lindgren C.M., Lokki M.L., Magnusson P.K., Mallick N.H., Mehra N., Meitinger T., Memon F.U., Morris A.P., Nieminen M.S., Pedersen N.L., Peters A., Rallidis L.S., Rasheed A., Samuel M., Shah S.H., Sinisalo J., Stirrups K.E., Trompet S., Wang L., Zaman K.S., Ardissino D., Boerwinkle E., Borecki I.B., Bottinger E.P., Buring J.E., Chambers J.C., Collins R., Cupples L.A., Danesh J., Demuth I., Elosua R., Epstein S.E., Esko T., Feitosa M.F., Franco O.H., Franzosi M.G., Granger C.B., Gu D., Gudnason V., Hall A.S., Hamsten A., Harris T.B., Hazen S.L., Hengstenberg C., Hofman A., Ingelsson E., Iribarren C., Jukema J.W., Karhunen P.J., Kim B.-J., Kooner J.S., Kullo I.J., Lehtimäki T., Loos R.J.F., Melander O., Metspalu A., März W., Palmer C.N., Perola M., Quertermous T., Rader D.J., Ridker P.M., Ripatti S., Roberts R., Salomaa V., Sanghera D.K., Schwartz S.M., Seedorf U., Stewart A.F., Stott D.J., Thiery J., Zalloua P.A., O’Donnell C.J., Reilly M.P., Assimes T.L., Thompson J.R., Erdmann J., Clarke R., Watkins H., Kathiresan S., McPherson R., Deloukas P., Schunkert H., Samani N.J., Farrall M. A comprehensive 1,000 Genomes-based genome-wide association meta-analysis of coronary artery disease. Nat. Genet. 2015; 47: 1121–1130. doi: 10.1038/ng.3396

17. van der Harst P., Verweij N. Identification of 64 Novel Genetic Loci Provides an Expanded View on the Genetic Architecture of Coronary Artery Disease. Circulat. Res. 2018; 122: 433–443. doi: 10.1161/CIRCRESAHA.117.312086

18. Dastani Z., Hivert M.-F., Timpson N., Perry J.R.B., Yuan X., Scott R.A., Henneman P., Heid I.M., Kizer J.R., Lyytikäinen L.-P., Fuchsberger C., Tanaka T., Morris A.P., Small K., Isaacs A., Beekman M., Coassin S., Lohman K.,Qi L., Kanoni S., Pankow J.S., Uh H.-W., Wu Y., BidulescuA., Rasmussen-Torvik L.J., Greenwood C.M.T., Ladouceur M., Grimsby J., Manning A.K., Liu C.-T., Kooner J., Mooser V.E., Vollenweider P., Kapur K.A., Chambers J., Wareham N.J., Langenberg C., Frants R., Willems-Vandijk K., Oostra B.A., Willems S.M., Lamina C., Winkler T.W., Psaty B.M., Tracy R.P., Brody J., Chen I., Viikari J., Kähönen M., Pramstaller P.P., Evans D.M., Pourcain B.St., Sattar N., Wood A.R., Bandinelli S., Carlson O.D., Egan J.M., Böhringer S., van Heemst D., Kedenko L., Kristiansson K., Nuotio M.-L., Loo B.-M., Harris T., Garcia M., Kanaya A., Haun M., Klopp N., WichmannH-E., Deloukas P., Katsareli E., Couper D.J., Duncan B.B., Kloppenburg M., Adair L.S., Borja J.B., DIAGRAM+ Consortium, MAGIC Consortium, GLGC Investigators, MuTHER Consortium, Wilson J.G., Musani S., Guo X., Johnson T., Semple R., Teslovich T.M., Allison M.A., Redline S., Buxbaum S.G., Mohlke K.L., Meulenbelt I., Ballantyne C.M., Dedoussis G.V., Hu F.B., Liu Y., Paulweber B., Spector T.D., Slagboom P.E., Ferrucci L., Jula A., Perola M., Raitakari O., Florez J.C., Salomaa V., Eriksson J.G., FraylingT.M., Hicks A.A., Lehtimäki T., Smith G.D., Siscovick D.S., Kronenberg F., van Duijn C., Loos R.J.F., Waterworth D.M., Meigs J.B., Dupuis J., Richards J.B. Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals. PLoS Genet. 2012; 8: e1002607. doi: 10.1371/journal.pgen.1002607

19. Chambers J.C., Zhang W., Sehmi J., Li X., Wass M.N., van der Harst P., Holm H., Sanna S., Kavousi M., Baumeister S.E., Coin L.J., Deng G., Gieger C., Heard-Costa N.L., Hottenga J.J., Kühnel B., Kumar V., Lagou V., Liang L., Luan J., Vidal P.M., Mateo Leach I., O’Reilly P.F., Peden J.F., Rahmioglu N., Soininen P., Speliotes E.K., Yuan X., Thorleifsson G., Alizadeh B.Z., Atwood L.D., Borecki I.B., Brown M.J., Charoen P., Cucca F., Das D., de Geus E.J., Dixon A.L., Döring A., Ehret G., Eyjolfsson G.I., Farrall M., Forouhi N.G., Friedrich N., Goessling W., Gudbjartsson D.F., Harris T.B., Hartikainen A.L., Heath S., Hirschfield G.M., Hofman A., Homuth G., Hyppönen E., Janssen H.L., Johnson T., Kangas A.J., Kema I.P., Kühn J.P., Lai S., Lathrop M., Lerch M.M., Li Y., Liang T.J., Lin J.P., Loos R.J., Martin N.G., Moffatt M.F., Montgomery G.W., Munroe P.B., Musunuru K., Nakamura Y., O’Donnell C.J., Olafsson I., Penninx B.W., Pouta A., Prins B.P., Prokopenko I., Puls R., Ruokonen A., Savolainen M.J., Schlessinger D., Schouten J.N., Seedorf U., Sen-Chowdhry S., Siminovitch K.A., Smit J.H., Spector T.D., Tan W., Teslovich T.M., Tukiainen T., Uitterlinden A.G., van der Klauw M.M., Vasan R.S., Wallace C., Wallaschofski H., Wichmann H.E., Willemsen G., Würtz P., Xu C., Yerges-Armstrong L.M.; Alcohol Genome-wide Association (AlcGen) Consortium; Diabetes Genetics Replication and Meta-analyses (DIAGRAM+) Study; Genetic Investigation of Anthropometric Traits (GIANT) Consortium; Global Lipids Genetics Consortium; Genetics of Liver Disease (GOLD) Consortium; International Consortium for Blood Pressure (ICBP-GWAS); Meta-analyses of Glucose and Insulin-Related Traits Consortium (MAGIC); Abecasis G.R., Ahmadi K.R., Boomsma D.I., Caulfield M., Cookson W.O., van Duijn C.M., Froguel P., Matsuda K., McCarthy M.I., Meisinger C., Mooser V., Pietiläinen K.H., Schumann G., Snieder H., Sternberg M.J.E., Stolk R.P., Thomas H.C., Thorsteinsdottir U., Uda M., Waeber G., Wareham N.J., Waterworth D.M., Watkins H., Whitfield J.B., Witteman J.C.M., Wolffenbuttel B.H.R., Fox C.S., Ala-Korpela M., Stefansson K., Vollenweider P., Völzke H., Schadt E.E., Scott J., Järvelin M.-R., Elliott P., Kooner J.S. Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma. Nat. Genet. 2011; 43: 1131–1138. doi: 10.1038/ng.970

20. Neuman M.G., Cohen L.B., Nanau R.M. Biomarkers in Nonalcoholic Fatty Liver Disease. Can. J. Gastroenterol. and Hepatol. 2014; 28: 607–618. doi: 10.1155/2014/757929

21. Ishizuka Y., Nakayama K., Ogawa A., Makishima S., Boonvisut S., Hirao A., Iwasaki Y., Yada T., Yanagisawa Y., Miyashita H., Takahashi M., Iwamoto S., Jichi Medical University Promotion Team of Large-Scale Human Genome Bank for All over Japan. TRIB1 downregulates hepatic lipogenesis and glycogenesis via multiple molecular interactions. J. Mol. Endocrinol. 2014; 52: 145–158. doi: 10.1530/JME-13-0243

22. Kitamoto A., Kitamoto T., Nakamura T., Ogawa Y., Yoneda M., Hyogo H., Ochi H., Mizusawa S., Ueno T., Nakao K., Sekine A., Chayama K., Nakajima A., Hotta K. Association of polymorphisms in GCKR and TRIB1 with nonalcoholic fatty liver disease and metabolic syndrome traits. Endocr. J. 2014; 61: 683–689. doi: 10.1507/endocrj.ej14-0052

23. Wei B., Liu Y., Li H., Peng Y., Luo Z. Effect of TRIB1 Variant on Lipid Profile and Coronary Artery Disease: A Systematic Review and Meta-Analysis. Cardiovasc. Ther. 2023; 9:2023:4444708. doi: 10.1155/2023/4444708

24. Malinowski D., Safranow K., Pawlik A. PON1 rs662, rs854560 and TRIB1 rs17321515, rs2954029 Gene Polymorphisms Are Associated with Lipid Parameters in Patients with Unstable Angina. Genes (Basel). 2024; 15 (7): 871. doi: 10.3390/genes15070871

25. Vargas-Alarcón G., Pérez-Méndez O., Posadas-Sánchez R., González-Pacheco H., Juárez-Cedillo T., Escobedo G., López-Olmos V., Fragoso J.M. TRIB1 and TRPS1 Gene Polymorphisms Are Associated with the Incidence of Acute Coronary Syndrome and Plasma Lipid Concentrations. Biology (Basel). 2025; 14 (6): 606. doi: 10.3390/biology14060606

26. Jiang J., Chen X., Li С., Du X., Zhou H. Polymorphisms of TRIB1 genes for coronary artery disease and stroke risk: A systematic review and meta-analysis. Gene, 2023; 880: 147613. doi: 10.1016/j.gene.2023.147613

27. Peasey A., Bobak M., Kubinova R., Malyutina S., Pajak A., Tamosiunas A., Pikhart H., Nicholson A., Marmot M. Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: Rationale and Design of the HAPIEE study. BMC Public Health. 2006; 6: 255. doi: 10.1186/1471-2458-6-255

28. Sambrook J., Russel D.W. Purification of nucleic acids by extraction with phenol: chloroform. CSH Protoc. 2006; 2006 (1): pdb.prot4455. doi: 10.1101/pdb.prot4455

29. Gafarov V., Gafarova A. Who programs: «register acute myocardial infarction», «monica» – dynamics acute cardiovascular accident at years 1977–2009 in general population aged 25–64 years in Russia. Russ. J. Cardiol. 2016; (4-eng): 129– 134. doi: 10.15829/1560-4071-2016-4-eng-129-134

30. Quiroz-Figueroa K., Vitali C., Conlon D.M., Millar J.S., Tobias J.W., Bauer R.C., Hand N.J., Rader D.J. TRIB1 regulates LDL metabolism through CEBPα-mediated effects on the LDL receptor in hepatocytes. J. Clin. Invest. 2021; 131 (22): e146775. doi: 10.1172/JCI146775

31. Karimi Z., Daneshmoghadam J., Ghaedi H., Khalili E., Panahi G., Shanaki M. Association of rs2954029 and rs6982502 Variants with Coronary Artery Disease by HRM Technique: A GWAS Replication Study in an Iranian Population. Rep. Biochem. Mol. Biol. 2022; 10 (4): 580–588. doi: 10.52547/rbmb.10.4.580

32. Zhang Q.-H., Yin R.-X., Chen W.-X., Cao X.-L., Wu J.-Z. TRIB1 and TRPS1 variants, G × G and G × E interactions on serum lipid levels, the risk of coronary heart disease and ischemic stroke. Sci. Rep. 2019; 9 (1): 2376. doi: 10.1038/s41598-019-38765-7

33. Semaev S., Shakhtshneider E., Shcherbakova L., Ivanoshchuk D., Orlov P., Malyutina S., Gafarov V., Ragino Y., Voevoda M. Associations of APOE Gene Variants rs429358 and rs7412 with Parameters of the Blood Lipid Profile and the Risk of Myocardial Infarction and Death in a White Population of Western Siberia. Curr. Issues. Mol. Biol. 2022; 44 (4): 1713–1724. doi: 10.3390/cimb44040118

34. Semaev S., Shakhtshneider E., Shcherbakova L., Orlov P., Ivanoshchuk D., Malyutina S., Gafarov V., Voevoda M., Ragino Y. Association of Common Variants of APOE, CETP, and the 9p21.3 Chromosomal Region with the Risk of Myocardial Infarction: A Prospective Study. Int. J. Mol. Sci. 2023; 24 (13): 10908. doi: 10.3390/ijms241310908

35. Semaev S.E., Shcherbakova L.V., Orlov P.S., Ivanoshchuk D.E., Malyutina S.K., Gafarov V.V., Voevoda M.I., Ragino Yu.I., Shakhtshneider E.V. Association of variants of the APOE, CETP genes and the 9P21.3 chromosomal region with coronary heart disease, myocardial infarction and acute heart failure. Ateroscleroz. 2024; 20 (2): 121–135. (In Russ.). doi: 10.52727/2078-256X-2024-20-2-121-135

36. Ershova A.I., Meshkov A.N., Kutsenko V.A., Vyatkin Yu.V., Kiseleva A.V., Sotnikova E.A., Limonova A.S., Garbuzova E.V., Muromtseva G.A., Zayihenoka M., Zharikova A.A., Ramensky V.E., Belova O.А., Rachkova S.A., Pokrovskaya M.S., Shalnova S.A., Boytsov S.A., Drapkina O.M. Validation of genetic risk scores for coronary artery disease, developed on European population samples, in Russian population. Cardiovasc. Ther. and Prevent. 2023; 22 (12): 3856. doi: 10.15829/1728-8800-2023-3856

37. Zaychenoka M., Meshkov A.N., Kiseleva A.V., Ershova A.I., Sotnikova E.A., Zharikova A.A., Vyatkin Yu.V., Mikhailina V.I., Bukaeva A.A., Pokrovskaya M.S., Ramenskiy V.E., Drapkina O.M. Use of polygenic risk scores for differential diagnostics for patients with clinical diagnosis of familial hypercholesterolemia. Cardiovasc. Ther. and Prevent. 2024; 23 (12): 4251. (In Russ.) doi: 10.15829/1728-8800-2024-4251 EDN: UYQMBM

38. Boytsov S.A., Drapkina O.M., Shlyakhto E.V., Konradi A.O., Balanova Yu.A., Zhernakova Yu.V., Metelskaya V.A., Oshchepkova E.V., Rotar O.P., Shalnova S.A. Epidemiology of Cardiovascular Diseases and their Risk Factors in Regions of Russian Federation (ESSE-RF) study. Ten years later. Cardiovasc. Ther. and Prevent. 2021; 20 (5): 3007. (In Russ.) doi: 10.15829/1728-8800-2021-3007

39. Zayichenoka M., Ershova A.I., Kiseleva A.V., Sotnikova E.A., Vyatkin Yu.V., Zharikova А.A., Pokrovskaya M.S., Shalnova S.A., Ramensky V.E., Meshkov A.N., Drapkina O.M. Search and replication of associations of genome variants with lipid levels in a Russian sample. Cardiovasc. Therapy and Prevent. 2023; 22 (12): 3871. (In Russ.) doi: 10.15829/1728-8800-2023-3871

40. Zaychenoka M., Ramenskiy V.E., Kiseleva A.V., Bukaeva A.A., Ershova A.I., Meshkov A.N., Drapkina O.M. Properties of incompletely penetrant cardiomyopathy-associated genome variants. Cardiovasc. Therapy and Prevent. 2024; 23 (12): 4262. (In Russ.) doi: 10.15829/1728-8800-20244262.