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Serum ADAMTS-9 Level in Newborn Babies with Congenital Heart DiseaseFunding None.
Objective A Disintegrin and Metalloproteinase with Thrombospondin-9 (ADAMTS-9), one of the ADAMTS enzymes, is expressed in all fetal tissues, unlike other ADAMTS enzymes, and is thus thought to play a role in fetal development. In this context, the objective of this study is to investigate the relationship between ADAMTS-9 activity and the development of congenital heart diseases (CHD) with a view to using ADAMTS-9 level as a biomarker for CHDs.
Study Design Newborns diagnosed with CHD and healthy newborns were included in the study as the CHD and control groups, respectively. Gestational age, maternal age, and mode of delivery information pertaining to the mothers and Apgar score and birthweight information pertaining to the newborns were recorded. Blood samples were taken from all newborns to determine their ADAMTS-9 levels in the first 24 hours of life.
Results Fifty-eight newborns with CHD and 46 healthy newborns were included in the study. Median ADAMTS-9 levels were 46.57 (interquartile range [IQR]: 33.31 [min: 26.92, max: 124.25]) and 23.36 (IQR: 5.48 [min: 11.7, max: 37.71]) ng/mL in the CHD and control groups, respectively. ADAMTS-9 levels in the CHD group were statistically significantly higher than in the control group (p = 0.000). ADAMTS-9 levels of the CHD and control groups were analyzed by the receiver operating characteristics curve. The area under the curve value for ADAMTS-9 levels of >27.86 ng/mL as the cut-off value for predicting the development of CHD in newborns was 0.836 (95% confidence interval [CI]: 0.753–0.900, p = 0.0001). ADAMTS-9 levels of >27.86 ng/mL were determined to predict the development of CHD in newborns with a sensitivity of 77.78% (95% CI: 65.5–87.38) and a specificity of 84.78% (95% CI: 71.1–93.60).
Conclusion In conclusion, it was found that the serum ADAMTS-9 levels were significantly higher in newborns with CHD than in healthy newborns. In parallel, ADAMTS-9 levels above a certain cut-off value were associated with CHD.
ADAMTS-9 is expressed in fetal tissues.
Its level increases in congenital heart diseases.
It can be used as a biochemical marker in diagnosis.
C.B., A.K., B.C., and C.T. conceptualized and designed the study, drafted the initial manuscript. C.T., I.K., and C.B. carried out the initial analyses, reviewed, and revised the manuscript. U.C., K.T., and M.K. supervised the statistics. C.T., K.T., and A.K. made critical revision of the manuscript for important intellectual content. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. The authors declare that all data were generated in-house and that no paper mill was used. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used
Received: 13 December 2022
Accepted: 06 July 2023
Accepted Manuscript online:
07 July 2023
Article published online:
14 August 2023
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- 1 Jenkins KJ, Correa A, Feinstein JA. et al; American Heart Association Council on Cardiovascular Disease in the Young. Noninherited risk factors and congenital cardiovascular defects: current knowledge: a scientific statement from the American Heart Association Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation 2007; 115 (23) 2995-3014
- 2 Pierpont ME, Brueckner M, Chung WK. et al; American Heart Association Council on Cardiovascular Disease in the Young; Council on Cardiovascular and Stroke Nursing; and Council on Genomic and Precision Medicine. Genetic basis for congenital heart disease: revisited: a scientific statement from the American Heart Association. Circulation 2018; 138 (21) e653-e711
- 3 Liu Y, Chen S, Zühlke L. et al. Global birth prevalence of congenital heart defects 1970-2017: updated systematic review and meta-analysis of 260 studies. Int J Epidemiol 2019; 48 (02) 455-463
- 4 Cowan JR, Ware SM. Genetics and genetic testing in congenital heart disease. Clin Perinatol 2015; 42 (02) 373-393 , ix
- 5 Hoang TT, Goldmuntz E, Roberts AE. et al. The congenital heart disease genetic network study: cohort description. PLoS One 2018; 13 (01) e0191319
- 6 Zaidi S, Brueckner M. Genetics and genomics of congenital heart disease. Circ Res 2017; 120 (06) 923-940
- 7 Stanton H, Melrose J, Little CB, Fosang AJ. Proteoglycan degradation by the ADAMTS family of proteinases. Biochim Biophys Acta 2011; 1812 (12) 1616-1629
- 8 Vázquez F, Hastings G, Ortega MA. et al. METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity. J Biol Chem 1999; 274 (33) 23349-23357
- 9 Colige A, Vandenberghe I, Thiry M. et al. Cloning and characterization of ADAMTS-14, a novel ADAMTS displaying high homology with ADAMTS-2 and ADAMTS-3. J Biol Chem 2002; 277 (08) 5756-5766
- 10 Fujikawa K, Suzuki H, McMullen B, Chung D. Purification of human von Willebrand factor-cleaving protease and its identification as a new member of the metalloproteinase family. Blood 2001; 98 (06) 1662-1666
- 11 Liu CJ, Kong W, Ilalov K. et al. ADAMTS-7: a metalloproteinase that directly binds to and degrades cartilage oligomeric matrix protein. FASEB J 2006; 20 (07) 988-990
- 12 Liu CJ, Kong W, Xu K. et al. ADAMTS-12 associates with and degrades cartilage oligomeric matrix protein. J Biol Chem 2006; 281 (23) 15800-15808
- 13 Somerville RP, Longpré JM, Apel ED. et al. ADAMTS7B, the full-length product of the ADAMTS7 gene, is a chondroitin sulfate proteoglycan containing a mucin domain. J Biol Chem 2004; 279 (34) 35159-35175
- 14 Clark ME, Kelner GS, Turbeville LA, Boyer A, Arden KC, Maki RA. ADAMTS9, a novel member of the ADAM-TS/ metallospondin gene family. Genomics 2000; 67 (03) 343-350
- 15 Kern CB, Wessels A, McGarity J. et al. Reduced versican cleavage due to Adamts9 haploinsufficiency is associated with cardiac and aortic anomalies. Matrix Biol 2010; 29 (04) 304-316
- 16 Jerves T, Beaton A, Kruszka P. The genetic workup for structural congenital heart disease. Am J Med Genet C Semin Med Genet 2020; 184 (01) 178-186
- 17 Jin SC, Homsy J, Zaidi S. et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat Genet 2017; 49 (11) 1593-1601
- 18 Manheimer KB, Richter F, Edelmann LJ. et al. Robust identification of mosaic variants in congenital heart disease. Hum Genet 2018; 137 (02) 183-193
- 19 Lockhart M, Wirrig E, Phelps A, Wessels A. Extracellular matrix and heart development. Birth Defects Res A Clin Mol Teratol 2011; 91 (06) 535-550
- 20 Zhang P, Shen M, Fernandez-Patron C, Kassiri Z. ADAMs family and relatives in cardiovascular physiology and pathology. J Mol Cell Cardiol 2016; 93: 186-199
- 21 Sandy JD, Westling J, Kenagy RD. et al. Versican V1 proteolysis in human aorta in vivo occurs at the Glu441-Ala442 bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4. J Biol Chem 2001; 276 (16) 13372-13378
- 22 Russell DL, Doyle KM, Ochsner SA, Sandy JD, Richards JS. Processing and localization of ADAMTS-1 and proteolytic cleavage of versican during cumulus matrix expansion and ovulation. J Biol Chem 2003; 278 (43) 42330-42339
- 23 Kintakas C, McCulloch DR. Emerging roles for ADAMTS5 during development and disease. Matrix Biol 2011; 30 (5-6): 311-317
- 24 Boesgaard TW, Gjesing AP, Grarup N. et al; EUGENE2 Consortium. Variant near ADAMTS9 known to associate with type 2 diabetes is related to insulin resistance in offspring of type 2 diabetes patients–EUGENE2 study. PLoS One 2009; 4 (09) e7236
- 25 Trombetta M, Bonetti S, Boselli ML. et al. PPARG2 Pro12Ala and ADAMTS9 rs4607103 as “insulin resistance loci” and “insulin secretion loci” in Italian individuals. The GENFIEV study and the Verona Newly Diagnosed Type 2 Diabetes Study (VNDS) 4. Acta Diabetol 2013; 50 (03) 401-408
- 26 Polfus LM, Smith JA, Shimmin LC. et al. Genome-wide association study of gene by smoking interactions in coronary artery calcification. PLoS One 2013; 8 (10) e74642
- 27 Franceschini N, Giambartolomei C, de Vries PS. et al; MEGASTROKE Consortium. GWAS and colocalization analyses implicate carotid intima-media thickness and carotid plaque loci in cardiovascular outcomes. Nat Commun 2018; 9 (01) 5141
- 28 Wei M, Pan H, Guo K. Association between plasma ADAMTS-9 levels and severity of coronary artery disease. Angiology 2021; 72 (04) 371-380
- 29 Li T, Peng J, Li Q, Shu Y, Zhu P, Hao L. The mechanism and role of ADAMTS protein family in osteoarthritis. Biomolecules 2022; 12 (07) 959