Hidatidiform Mol Gebeliği olan Kadınlarda Plazma Serbest Amino Asit ve Karnitin Düzeyleri: Vaka Kontrol Çalışması

Öz

Amaç: Hidatidiform mol (HM)'li gebe kadınlarda plazma serbest amino asit (FAA) ve karnitin düzeylerini belirlemek. Materyal ve metod: Çalışmaya 23 HM'li gebe ve kontrol grubu olarak 24 sağlıklı gebe dahil edildi. FAA ve karnitin konsantrasyonları, sıvı kromatografisi/tandem kütle spektrometrisi (LC-MS) kullanılarak plazmada ölçüldü. Bulgular: İncelenen 14 amino asitten alanin, arginin ve valin düzeyleri HM grubunda sağlıklı gruba göre anlamlı derecede düşüktü (sırasıyla p = 0,019, p = 0,009 ve p = 0,03). Ek olarak, incelenen 27 karnitinden birkaç karnitin, C8DC, C16:1 ve C18, HM grubunda kontrol grubuna göre önemli ölçüde daha yüksekti (sırasıyla p = 0,021, p = 0,03 ve p = 0,021). Sonuç: Bu çalışma, bazı FAA'lerin plazma seviyesindeki azalmanın ve bazı karnitinlerin de plazma düzeylerindeki artışın HM patogenezinde etkili olabileceğini ortaya koydu.

Anahtar Kelimeler

• karnitin
• serbest amino asit
• gebelik
• hidatidiform mol

Plasma Free Amino Acid and Carnitine Levels in Pregnant Women with Hydatidiform Mole: A Case-Controlled Study

Öz

Background: To determine plasma free amino acid (FAA) and carnitine levels in pregnant women with hydatidiform mole (HM). Materials and Methods: Twenty-three pregnant women with HM, and 24 healthy pregnant wo-men as controls were enrolled in the study. FAA and carnitine concentrations were measured in plasma using liquid chromatography/tandem mass spectrometry (LC-MS). Results: The levels of alanine, arginine, and valine from the 14 amino acids examined were signif-icantly lower in the HM group than in the healthy group (p = 0.019, p = 0.009, and p = 0.03, respec-tively). In addition, several carnitines, C8DC, C16:1, and C18, of the 27 carnitines examined were significantly higher in the HM group than in the control group (p = 0.021, p = 0.03, and p = 0.021, respectively). Conclusions: This study demonstrated that a decrease in some plasma FAAs and an increase in some plasma carnitine levels might be effective in the pathogenesis of HM.

Anahtar Kelimeler

• carnitine
• free amino acid
• hydatidiform mole
• pregnancy

Kaynakça

1. 1. Landolsi H, Missaoui N, Brahem S, Hmissa S, Gribaa M, Yacoubi MT. The usefulness of p57(KIP2) immunohistoc-hemical staining and genotyping test in the diagnosis of the hydatidiform mole. Pathol Res Pract. 2011 Aug 15;207(8):498-504.
2. 2. Shamshiri Milani H, Abdollahi M, Torbati S, Asbaghi T, Azargashb E. Risk Factors for Hydatidiform Mole: Is Hus-band’s Job a Major Risk Factor? Asian Pac J Cancer Prev. 2017 Oct 26;18(10):2657-62.
3. 3. Shih IeM. Gestational trophoblastic neoplasia--pathogenesis and potential therapeutic targets. Lancet Oncol. 2007 Jul;8(7):642-50.
4. 4. Hui P, Buza N, Murphy KM, Ronnett BM. Hydatidiform Moles: Genetic Basis and Precision Diagnosis. Annu Rev Pathol. 2017 Jan 24;12:449-85.
5. 5. Lurain JR. Gestational trophoblastic disease I: epidemio-logy, pathology, clinical presentation and diagnosis of ges-tational trophoblastic disease, and management of hyda-tidiform mole. Am J Obstet Gynecol. 2010;203(6):531-9.
6. 6. McGarry JD, Brown NF. The mitochondrial carnitine pal-mitoyltransferase system. From concept to molecular analysis. Eur J Biochem. 1997;244(1):1-14.
7. 7. Vaz FM, Wanders RJ. Carnitine biosynthesis in mammals. Biochem J. 2002;361(3)417-29.
8. 8. Grube M, Meyer Zu Schwabedissen H, Draber K, Präger D, Möritz KU, Linnemann K, et al. Expression, localization, and function of the carnitine transporter octn2 (slc22a5) in human placenta. Drug Metab Dispos. 2005;33(1):31-7.

9. 9. Fiehn O. Combining genomics, metabolome analysis, and biochemical modelling to understand metabolic networks. Comp Funct Genomics. 2001;2(3):155-68.
10. 10. Lai HS, Lee JC, Lee PH, Wang ST, Chen WJ. Plasma free amino acid profile in cancer patients. Semin Cancer Biol. 2005;15(4):267–76.
11. 11. Okamoto N, Miyagi Y, Chiba A, Akaike M, Shiozawa M, Imaizumi A, et al. Diagnostic modeling with differences in plasma amino acid profiles between non-cachectic colo-rectal/breast cancer patients and healthy individuals. Int J Med Med Sci. 2009;1:1–8.
12. 12. Roux C, Riganti C, Borgogno SF, Curto R, Curcio C, Catan-zaro V, et al. Endogenous glutamine decrease is associa-ted with pancreatic cancer progression. Oncotarget. 2017;8(56):95361.
13. 13. Camelo JS Jr, Jorge SM, Martinez FE. Amino acid composi-tion of parturient plasma, the intervillous space of the placenta and the umbilical vein of term newborn infants. Braz J Med Biol Res. 2004;37(5):711-7.
14. 14. La Marca G, Malvagia S, Pasquini E, Innocenti M, Fernan-dez MR, Donati MA, et al. The inclusion of succinylacetone as marker for tyrosinemia type I in expanded newborn screening programs. Rapid Communications in Mass Spectrometry. 2008; 22(6):812-8.
15. 15. Azzari C, La Marca G, Resti M. Neonatal screening for severe combined immunodeficiency caused by an adeno-sine deaminase defect: a reliable and inexpensive method using tandem mass spectrometry. Journal of Allergy and Clinical Immunology. 2011;127(6):1394-9.
16. 16. Cederblad G, Fahraeus L, Lindgren K. Plasma carnitine and renal carnitine clearance during pregnancy. Am J Clin Nutr. 1986;44(3):379-83.
17. 17. Cho SW, Cha YS. Pregnancy increases urinary loss of carni-tine and reduces plasma carnitine in Korean women. Br J Nutr. 2005;93(5):685–91.
18. 18. Ringseis R, Hanisch N, Seliger G, Eder K. Low availability of carnitine precursors as a possible reason for the dimi-nished plasma carnitine concentrations in pregnant wo-men. BMC Pregnancy Childbirth. 2010;25:10-7.
19. 19. Bai M, Zeng Q, Chen Y, Chen M, Li P, Ma Z, et al. Maternal plasma L-carnitine reduction during pregnancy is mainly attributed to OCTN2 mediated placental uptake and does not result in maternal hepatic fatty acid β-oxidation decli-ne. Drug Metab Dispos. 2019;47(6):582-91.
20. 20. Miyagi Y, Higashiyama M, Gochi A, Akaike M, Ishikawa T, Miura T, et al. Plasma free amino acid profiling of five ty-pes of cancer patients and its application for early detec-tion. PLoS One. 2011;6(9):e24143.
21. 21. Virgiliou C, Gika HG, Witting M, Bletsou AA, Athanasiadis A, Zafrakas M, et al. Amniotic Fluid and Maternal Serum Metabolic Signatures in the Second Trimester Associated with Preterm Delivery. J Proteome Res. 2017;16(2):898-910.
22. 22. Chorell E, Hall UA, Gustavsson C, Berntorp K, Puhkala J, Luoto R, et al. Pregnancy to postpartum transition of se-rum metabolites in women with gestational diabetes. Metabolism. 2017;72:27-36.
23. 23. Pappa KI, Vlachos G, Theodora M, Roubelaki M, Angelidou K, Antsaklis A. Intermediate metabolism in association with the amino acid profile during the third trimester of normal pregnancy and diet-controlled gestational diabe-tes. Am J Obstet Gynecol. 2007;196(1):1-5.
24. 24. Saglik A, Koyuncu I, Gonel A, Yalcin H, Adibelli FM, Toptan M. Metabolomics analysis in pterygium tissue. Int Opht-halmol. 2019;39(10):2325-33.
25. 25. Jian Liu, Sanren Lin, Zhengpeng Li, Liya Zhou, Xiue Yan, Yan Xue, et al. Free amino acid profiling of gastric juice as a method for discovering potential biomarkers of early gastric cancer. Int J Clin Exp Pathol. 2018;11(5):2323-36.
26. 26. Rigamonti AE, Leoncini R, De Col A, Tamini S, Cicolini S, Abbruzzese L, et al. The Appetite-Suppressant and GLP-1-Stimulating Effects of Whey Proteins in Obese Subjects are Associated with Increased Circulating Levels of Speci-fic Amino Acids. Nutrients. 2020;12(3):775.
27. 27. Yamada H, Sata F, Saijo Y, Kishi R, Minakami H. Genetic factors in fetal growth restriction and miscarriage. Semin Thromb Hemost. 2005;31(3):334-45.