Transforming Growth Factor Beta Receptor 3 Haplotypes in Sickle Cell Disease Are Associated with Lipid Profile and Clinical Manifestations

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2020 Nov 5

PMID 33149723

Citations 2

Authors

Rayra P Santiago

Camylla V B Figueiredo

Luciana M Fiuza

Setondji C M A Yahouedehou

Rodrigo M Oliveira

Milena M Aleluia

Suellen P Carvalho

Cleverson A Fonseca

Valma M L Nascimento

Larissa C Rocha

Caroline C Guarda

Marilda S Goncalves

Affiliations

Soon will be listed here.

Abstract

Individuals with sickle cell disease (SCD) present both chronic and acute inflammatory events. The TGF- pathway is known to play a role in immune response, angiogenesis, inflammation, hematopoiesis, vascular inflammation, and cell proliferation. Polymorphisms in the transforming growth factor-beta receptor 3 () gene have been linked to several inflammatory diseases. This study investigated associations between two haplotypes and classical laboratory parameters, as well as clinical manifestations, in SCD. We found that individuals with the GG haplotype presented higher levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides, non-HDL cholesterol, total proteins, and globulin than individuals with non-GG haplotypes. In addition, the GG haplotype was associated with a previous history of pneumonia. Individuals with the CGG haplotype presented increased plateletcrit, TC, LDL-C levels, and non-HDL cholesterol. The CCG haplotype was also associated with a previous history of pneumonia. Our findings suggest that individuals with the GG and CGG haplotypes of present important alterations in lipid profile.

Citing Articles

A 5-transcript signature for discriminating viral and bacterial etiology in pediatric pneumonia.

Viz-Lasheras S, Gomez-Carballa A, Pardo-Seco J, Bello X, Rivero-Calle I, Dacosta A iScience. 2025; 28(2):111747.

PMID: 39906557 PMC: 11791257. DOI: 10.1016/j.isci.2025.111747.

Genetic Variation and Sickle Cell Disease Severity: A Systematic Review and Meta-Analysis.

Kirkham J, Estepp J, Weiss M, Rashkin S JAMA Netw Open. 2023; 6(10):e2337484.

PMID: 37851445 PMC: 10585422. DOI: 10.1001/jamanetworkopen.2023.37484.

Does TGFBR3 Polymorphism Increase the Risk of Silent Cerebral Infarction in Egyptian Children with Sickle Cell Disease?.

Hassab H, Hanafi M, ElBeheiry A, Hassan M, El Chazli Y Indian J Pediatr. 2022; 90(2):146-152.

PMID: 35781614 PMC: 9842542. DOI: 10.1007/s12098-022-04181-5.

References

Liu J, Sempos C, Donahue R, Dorn J, Trevisan M, Grundy S . Joint distribution of non-HDL and LDL cholesterol and coronary heart disease risk prediction among individuals with and without diabetes. Diabetes Care. 2005; 28(8):1916-21. DOI: 10.2337/diacare.28.8.1916. View

Kato G, McGowan V, Machado R, Little J, Taylor 6th J, Morris C . Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2005; 107(6):2279-85. PMC: 1895723. DOI: 10.1182/blood-2005-06-2373. View

Blobe G, Schiemann W, Pepin M, Beauchemin M, Moustakas A, Lodish H . Functional roles for the cytoplasmic domain of the type III transforming growth factor beta receptor in regulating transforming growth factor beta signaling. J Biol Chem. 2001; 276(27):24627-37. DOI: 10.1074/jbc.M100188200. View

Gao X, Lee H, Lummertz da Rocha E, Zhang C, Lu Y, Li D . TGF-β inhibitors stimulate red blood cell production by enhancing self-renewal of BFU-E erythroid progenitors. Blood. 2016; 128(23):2637-2641. PMC: 5146747. DOI: 10.1182/blood-2016-05-718320. View

Williams T, Thein S . Sickle Cell Anemia and Its Phenotypes. Annu Rev Genomics Hum Genet. 2018; 19:113-147. PMC: 7613509. DOI: 10.1146/annurev-genom-083117-021320. View

Ephraim R, Adu P, Ake E, Agbodzakey H, Adoba P, Cudjoe O . Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis. J Lipids. 2017; 2016:7650530. PMC: 5203913. DOI: 10.1155/2016/7650530. View

Bond L, Hatty S, Horn M, Dick M, Meire H, Bellingham A . Gall stones in sickle cell disease in the United Kingdom. Br Med J (Clin Res Ed). 1987; 295(6592):234-6. PMC: 1247079. DOI: 10.1136/bmj.295.6592.234. View

Sebastiani P, Ramoni M, Nolan V, Baldwin C, Steinberg M . Genetic dissection and prognostic modeling of overt stroke in sickle cell anemia. Nat Genet. 2005; 37(4):435-40. PMC: 2896308. DOI: 10.1038/ng1533. View

Ashley-Koch A, Elliott L, Kail M, De Castro L, Jonassaint J, Jackson T . Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood. 2008; 111(12):5721-6. PMC: 2424164. DOI: 10.1182/blood-2007-02-074849. View

10.

Zhang Y, Wu N, Li S, Zhu C, Guo Y, Qing P . Non-HDL-C is a Better Predictor for the Severity of Coronary Atherosclerosis Compared with LDL-C. Heart Lung Circ. 2016; 25(10):975-81. DOI: 10.1016/j.hlc.2016.04.025. View

11.

Boekholdt S, Arsenault B, Mora S, Pedersen T, LaRosa J, Nestel P . Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012; 307(12):1302-9. DOI: 10.1001/jama.2012.366. View

12.

Vichinsky E, Neumayr L, Earles A, Williams R, Lennette E, Dean D . Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000; 342(25):1855-65. DOI: 10.1056/NEJM200006223422502. View

13.

Carvalho M, Araujo-Santos T, Reis J, Rocha L, Cerqueira B, Luz N . Inflammatory mediators in sickle cell anaemia highlight the difference between steady state and crisis in paediatric patients. Br J Haematol. 2017; 182(6):933-936. DOI: 10.1111/bjh.14896. View

14.

Ebert E, Nagar M, Hagspiel K . Gastrointestinal and hepatic complications of sickle cell disease. Clin Gastroenterol Hepatol. 2010; 8(6):483-9. DOI: 10.1016/j.cgh.2010.02.016. View

15.

Pitanga T, Oliveira R, Zanette D, Guarda C, Santiago R, Santana S . Sickle red cells as danger signals on proinflammatory gene expression, leukotriene B4 and interleukin-1 beta production in peripheral blood mononuclear cell. Cytokine. 2016; 83:75-84. DOI: 10.1016/j.cyto.2016.03.016. View

16.

Taylor S, Shacks S, Qu Z, Wiley P . Type 2 cytokine serum levels in healthy sickle cell disease patients. J Natl Med Assoc. 1998; 89(11):753-7. PMC: 2608277. View

17.

Kato G, Piel F, Reid C, Gaston M, Ohene-Frempong K, Krishnamurti L . Sickle cell disease. Nat Rev Dis Primers. 2018; 4:18010. DOI: 10.1038/nrdp.2018.10. View

18.

Martins R, Soares R, de Vito F, Barbosa V, Silva S, Moraes-Souza H . Cholelithiasis and its complications in sickle cell disease in a university hospital. Rev Bras Hematol Hemoter. 2017; 39(1):28-31. PMC: 5339364. DOI: 10.1016/j.bjhh.2016.09.009. View

19.

Aleluia M, Fonseca T, Souza R, Neves F, da Guarda C, Santiago R . Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization, laboratory biomarkers and genetic profiles. BMC Hematol. 2017; 17:15. PMC: 5602866. DOI: 10.1186/s12878-017-0087-7. View

20.

Elliott L, Ashley-Koch A, De Castro L, Jonassaint J, Price J, Ataga K . Genetic polymorphisms associated with priapism in sickle cell disease. Br J Haematol. 2007; 137(3):262-7. DOI: 10.1111/j.1365-2141.2007.06560.x. View