MİTOKONDRİYAL HASTALIK NEDENİYLE TETKİK EDİLEN HASTALARDA M.16189T>C DEĞİŞİKLİĞİNİN METABOLİK SENDROM AÇISINDAN İNCELENMESİ

Yıl 2022, Cilt: 23 Sayı: 3, 322 - 325, 18.07.2022

Aslı İnci , Filiz Başak Cengiz Ergin , İlyas Okur , Gürsel Biberoğlu Leyla Tümer Fatih Süheyl Ezgü

https://doi.org/10.18229/kocatepetip.928450

Öz

AMAÇ: Metabolik sendrom, obezite, yüksek düzeyde düşük yoğunluklu kolesterol düzeyi (LDL), trigliserit düzeyi (TG) ve insuline duyarlılık ile karakterize olan günümüzde sıklığı giderek artan bir bozukluktur. Metabolik sendromun etiyopatogenezinde hem genetik hem de çevresel nedenlerin rol oynadığı bilinmektedir. Özellikle mitokondriyal DNA’da oluşan m.16189T>C değişikliğinin bu hastalıkla ilişkili olduğu gösterilmiştir. Bu çalışmada mitokondriyal hastalık şüphesi ile başvuran hastalarda saptanan m.16189T>C değişikliğinin klinik ve laboratuvar bulgularının incelenmesi amaçlanmıştır.
GEREÇ VE YÖNTEM: Kliniğimize 2019 - 2020 yılları arasında mitokondriyal hastalık şüphesi ile gelen hastalardan m.16189T>C değişikliği olan hastalar çalışmaya alınmıştır. Hastaların klinik ve laboratuvar bulguları mitokondriyal hastalık şüphesi taşıması nedeniyle periferik kandan mitokondriyal DNA izolasyonu yapılmıştır. Yeni nesil DNA dizileme ile tüm mitokondriyal genom DNA dizi analizi yapılarak m.16189T>C değişikliği olan hastalar saptanarak çalışmaya dahil edilmiştir. Bu hastaların klinik ve laboratuvar bulguları metabolik sendrom açısından incelenmiştir.
BULGULAR: 1 yıllık süre içinde 55 hastanın 11’inde mitokondriyal genom analizinde m.16189T>C değişikliği saptanmıştır (%20). Fizik muayene bulgularında, hiçbir hastada fazla tartı ve obezite saptanmamıştır. Hastaların glukoz, LDL ve trigliserit düzeyleri normal aralıkta bulunmuştur.
SONUÇ: Hasta grubumuzda oldukça yüksek oranda saptanan bu değişikliğin metabolik sendrom ile ilişkisi gösterilememiş ve polimorfizm olarak değerlendirilmiştir. Ancak mitokondriyal hastalık şüphesi ile gelen bu hastaların kullandığı ilaçların, beslenme şekillerinin ve hastalığın patofizyolojisinin bu metabolik sendromu etkileyen çevresel faktörler olabileceği ön görülebilir.

Anahtar Kelimeler

Metabolik sendrom, Mitokondriyal hastalık, Mitokondriyal genom analizi, M.16189T>C.

Destekleyen Kurum

Yoktur

Proje Numarası

Yoktur

Teşekkür

Tüm çalışma arkadaşlarımıza, hastalarıma ve ailelerine teşekkür ederiz

INVESTIGATION OF M.16189T> C VARIANT IN TERMS OF METABOLIC SYNDROME IN PATIENTS EXAMINED FOR MITOCHONDRIAL DISEASE

Öz

OBJECTIVE: Metabolic syndrome is an increasingly common disorder, characterized by obesity, high low-density cholesterol level (LDL), triglyceride level (TG), and insulin sensitivity. It is known that both genetic and environmental factors play a role in the etiopathogenesis of metabolic syndrome. It has shown that the m.16189T>C variant that occurs mainly in mitochondrial DNA is associated with this disease. In this study, it was aimed to examine the clinical and laboratory findings of m.16189T>C change detected in patients who applied with suspected mitochondrial disease.
MATERIAL AND METHODS: Patients with a change in m.16189T>C among the patients who came to our clinic with the suspicion of mitochondrial disease between 2019-2020 were included in the study. Mitochondrial DNA was isolated from peripheral blood because the clinical and laboratory findings of the patients were suspicious of mitochondrial disease. New generation DNA sequencing and whole mitochondrial genome DNA sequence analysis were performed and patients with m.16189T>C changes were determined and included in the study. Clinical and laboratory findings of these patients were examined in terms of metabolic syndrome.
RESULTS: M.16189T>C variant was found in mitochondrial genome analysis in 11 of 55 patients (20%). In the physical examination findings, excessive weight and obesity were not detected in any of the patients. The glucose, LDL, and triglyceride levels of the patients were within the normal range.
CONCLUSIONS: This change, which was detected at a high rate in our patient group, could not be associated with metabolic syndrome and was evaluated as a polymorphism. However, it can be predicted that the drugs used by these patients who had a suspicion of mitochondrial disease, their diet, and the pathophysiology of the disease may be the environmental factors affecting the metabolic syndrome.

Anahtar Kelimeler

Metabolic syndrome, Mitochondrial disease, Mitochondrial genome analysis, M.16189T>C .

Proje Numarası

Yoktur

Kaynakça

• 1. Kozan O, Oguz A, Abaci A, et al. Prevalence of the metabolic syndrome among Turkish adults. Eur J Clin Nutr. 2007; 61(4): 548-53.
• 2. Alberti KG and Zimmet, PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med. 1998;(15):539-53.
• 3. Paul L, Huang A. comprehensive definition for metabolic syndrome. Disease Models & Mechanisms. 2009;(2):231-7.
• 4. Ordovas JM. Genetic links between diabetes mellitus and coronary atherosclerosis. Curr Atheroscler Rep. 2007;(9):204-10.
• 5. Taylor RW, Turnbull DM. Mitochondrial DNA mutations in human disease. Nat Rev Genet. 2005; (6): 389-402.
• 6. Palmieri VO, De Rasmo D, Signorile A, et al. T16189C mitochondrial DNA variant is associated with metabolic syndrome in Caucasian subjects Nutrition. 2011;27(7-8):773-7.
• 7. Saldana-Rivera, E, Careaga-Castilla MJ, Olvera-Cardenas GD, et al. Mitochondrial T16189C polymorphism Is associated with metabolic syndrome in the Mexican population Disease Markers. 2018;(25):2018:3981315.
• 8. Robinson JT, Thorvaldsdóttir H, Winckler W, et al. Integrative genomics viewer. Nat Biotechnol. 2011;(29):24–6.
• 9. Lott MT, Leipzig JN, Derbeneva O, et al. mtDNA variation and analysis using MITOMAP and MITOMASTER. Current Protocols in Bioinformatics. 2013;1(123): 1-26.
• 10. Liou CW, Lin TK, Huei Weng H, et al. A common mitochondrial DNA variant and increased body mass index as associated factors for development of type 2 diabetes: Additive effects of genetic and environmental factors. J Clin Endocrinol Metab. 2007;92(1):235-9.
• 11. Ji L, Gao L, Han X. Association of 16189 variant (T-->C transition) of mitochondrial DNA with genetic predisposition to type 2 diabetes in Chinese populations. Zhonghua Yi Xue Za Zhi. 2001;(81): 711-4.
• 12. Chinnery PF, Elliott HR, Patel S, et al. Role of the mitochondrial DNA 16184-16193 poly-C tract in type 2 diabetes. Lancet. 2005;(366):1650-1.
• 13. Gill-Randall R, Sherratt EJ, Thomas AW, et al. Analysis of a polycytosine tract and heteroplasmic length variation in the mitochondrial DNA D-loop of patients with diabetes, MELAS syndrome and race-matched controls. Diabet Med. 2001;(18):413-16.
• 14. Das S, Bennett AJ, Sovio U, et al. Detailed analysis of variation at and around mitochondrial position 16189 in a large Finnish cohort reveals no significant associations with early growth or metabolic phenotypes at age 31 years. J Clin Endocrinol Metab. 2007;(92): 3219-23.
• 15. Wang PW, Lin TK, Weng SW, et al. Mitochondrial DNA variants in the pathogenesis of type 2 diabetes - relevance of asian population studies. Rev Diabet Stud. 2009;(6): 237-46.