Filiz Başak CENGİZ ERGİN, Aslı İNCİ, İlyas OKUR, Gursel Biberoglu, Leyla TÜMER, Fatih Süheyl EZGÜ

m.3010G>A Değişikliğinin Türk Populasyonunda Siklik Kusma Sendromuna Etkisi

Giriş ve Amaç: Siklik kusma sendromu (SKS) sık görülen gastrointestinal fonksiyonel bir düzensizliktir. Gastrointestinal fonksiyonel düzensizliklerin mitokondriyal polimorfizmlerle ilişkili olduğu gösterilmiştir. Bu çalışmada, m.3010G>A değişikliğini taşıyan hastalarda klinik bulguların incelenmesi amaçlanmıştır. Gereç ve Yöntemler: Kliniğimize mitokondriyal hastalık şüphesi ile gelen 55 hastadan, periferik kandan mitokondriyal DNA izolasyonu yapılmıştır. Yeni nesil DNA dizileme ile tüm mitokondriyal genom DNA dizi analizi yapılarak m.3010G>A değişikliği olan hastalar saptanmıştır. Bu hastalarda klinik bulgular incelenmiştir. Bulgular: Toplam 55 hastada yapılan mitokondriyal genom analizinde altı farklı hastada m.3010G>A değişikliği saptanmıştır. m.3010G>A değişikliği saptanan bu hasta grubunda SKS ile ilgili klinik bulgular saptanmamıştır. Sonuç: Daha önce yapılan çalışmalarda m.3010G>A değişikliğinin SKS ile ilişkili olabileceği gösterilmiş olsa da bizim çalışmamızda katılan hastalarda bu bulgular bulunmamaktadır. Yine de SKS’nin ileri yaşlarda da ortaya çıkabileceği göz önünde bulundurulmalı ve yakın takip edilmelidir.

The Effect of m.3010G> A Variant on Cyclic Vomiting Syndrome in Turkish Population

Objective: Cyclic vomiting syndrome (CVS) is a common gastrointestinal functional disorder. It has been shown that gastrointestinal functional disorders are associated with mitochondrial polymorphisms. In this study, we aimed that examine the clinical findings in patients with the m.3010G>A polymorphism. Materials and Methods: Mitochondrial DNA isolation was performed from peripheral blood from 55 patients who came to our clinic with suspicion of mitochondrial metabolic disease. Patients with m.3010G>A polymorphism were identified by performing whole mitochondrial genome DNA sequencing via Next-Generation DNA sequencing. These patients were examined for their clinical findings. Results: The mitochondrial genome analysis was performed on 55 patients in total, m.3010G>A polymorphism was detected in six different patients. There were no clinical findings related to CVS in this patient group with m.3010G>A polymorphism. Conclusions: Although it has been shown in previous studies that the m.3010G>A polymorphism could be associated with CVS these findings were not present in the patients participating in our study. Nevertheless, it should retain that CVS can occur in late-onset.

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Boles, R.G, Zaki, E.A, Lavenbarg, T, Hejazi, R, Foran, P, Freeborn, J, Trilokekar,, S, McCallum R, Are pediatric and adult-onset cyclic vomiting syndrome (CVS) biologically different conditions? Relationship of adult-onset CVS with the migraine and pediatric CVS- associated common mtDNA polymorphisms 16519T and 3010A, Neurogastroenterology & Motility, 2009, 21(9), 936-e72.
Wang, Q, Ito, M, Adams, K, Li, B.U.K, Klopstock, T, Maslim, A, Higashimoto, T, et al., Mitochondrial DNA Control Region Sequence Variation in Migraine Headache and Cyclic Vomiting Syndrome, American Journal of Medical Genetics, 2004, 131A, 50–58.
Li, B.U.K, Lefevre, F, Chelimsky, G.G, Boles, R.G, Nelson, S.P, Lewis, D.W, Linder, S.L, Issenman, R.M, Rudolph, CD, North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition Consensus Statement on the Diagnosis and Management of Cyclic Vomiting Syndrome, Journal of Pediatric Gastroenterology and Nutrition, 2008, 47, 379–393.
Fleisher, R.D, Gornowicz, B, Adams, K, Burch, R, Feldman, E.J, Cyclic Vomiting Syndrome in 41 adults: the illness, the patients, and problems of management, BMC Medicine, 2005, 21, 3, 20.
Raucci, U, Borrelli, O, Di Nardo, G, Tambucci, R, Pavone, P, Salvatore, S, et al., Cyclic Vomiting Syndrome in Children. Frontiers in Neurology, 2020, 2, 11, 583425.
Ertekin, V, Selimoğlu, M.A, Altnkaynak, S, Prevalence of cyclic vomiting syndrome in a sample of Turkish school children in an urban area, Journal of Clinical Gastroenterology, 2006, 40(10), 896-8.
Boles, R.G, Powers, A.L, Adams, K, Cyclic vomiting syndrome plus, Journal of Child Neurology, 2006, 21, 182–8.
Camilleri, M, Carlson, P, Zinsmeister, A.R, McKinzie, S, Busciglio, I, Burton, D, Zaki, E.A, and Boles, R.G, Mitochondrial DNA and gastrointestinal motor and sensory functions in health and functional gastrointestinal disorders, American Journal of Physiology-Gastrointestinal and Liver Physiology, 2009, 296, G510–G516.
Zaki, E.A, Freilinger, T, Klopstock, T, Baldwin, E.E, Heisner, K.R.U, Adams, K, Dichgans, M, Wagler, S, Boles, R.G, Two common mitochondrial DNA polymorphisms are highly associated with migraine headache and cyclic vomiting syndrome, Cephalalgia, 2009, 29(7), 719-28.
Lott, M.T, Leipzig, J.N, Derbeneva, O, Xie, H.M, Chalkia, D, Sarmady, M, et al., mtDNA variation and analysis using MITOMAP and MITOMASTER, Current Protocols in Bioinformatics, 2013, 1(123), 1.23.1-26, URL: http://www.mitomap.org
Robinson, J.T, Thorvaldsdóttir, H, Winckler, W et al., Integrative genomics viewer, Nature Biotechnology, 2011, 29, 24–26.
Boles, R.G, Zaki, E.A, Kerr, J.R, Das, K, Biswas, S, Gardner, A, Increased prevalence of two mitochondrial DNA polymorphisms in functional disease: Are we describing different parts of an energy-depleted elephant? Mitochondrion, 2015, Pages 1-6.
Lee J, Wong, S.A, Li, B.U.K, Boles, R.G, Next Gen nuclear DNA sequencing in cyclic vomiting syndrome reveals a significant association with the stress-induced calcium channel (RYR2), Neurogastroenterology & Motility, 2015, 27, 990–996.
Hasler, W.L, Levinthal, D.J, Tarbell, S.E, Adams, K.A, Li, B.U.K, Issenman, R.M, et al., Neurogastroenterology & Motility, 2019, 31(Suppl. 2), e13607.
Bhandari, S, Jha, P, Thakur, A, Kar, A, Gerdes, H, Venkatesan, T, Cyclic vomiting syndrome: epidemiology, diagnosis, and treatment, Clinical Autonomic Research, 2018, 28, 203–209.