Povezanost polimorfizma PAX3 i TMTC2 gena sa promenama morfologije lica nakon ekscizije tumora kože
Sažetak
Uvod/Cilj. Grupa gena, poznata pod nazivom PAX (eng. paired box), ima velikog udela u organogenezi, kao i u održavanju normalne funkcije izvesnih ćelija nakon rođenja. Pored ovih gena, uticaj na organogenezu, na ćelijskom nivou, ima i transmembransko-tetratrikopeptidna grupa gena (TMTC). Pod pojmom polimorfizam u genomu čoveka podrazumevaju se varijacije u naslednoj osnovi koje se javljaju u humanim populacijama, prisutnost dva ili više različitih alela jednog gena u populaciji. Cilj rada bio je da se utvrdi da li postoji povezanost polimorfizma PAX3 i TMTC2 gena sa promenom morfologije lica nakon ekscizije tumora kože i postekscizione direktne suture. Metode. Istraživanjem je bilo obuhvaćeno 130 ispitanika, oba pola, starijih od 50 godina, kod kojih je postavljena medicinska indikacija za hiruršku elipsastu eksciziju tumora kože lica. DNK je izolovana iz 5mL periferne krvi. Polimorfizmi gena analizirani su predizajniranim single nucleotide polymorphisms (SNP) esejima, metodom alelske diskriminacije na REAL-TIME aparatu. Ispitanici su skenirani laser skenerom preoperativno, kao i sedam dana i 90 dana postoperativno, kako bi se za svakog ispitanika dobile x, y i z koordinate pet kefalometrijskih tačaka na licu, koje su određivale oblik medijalne obrazne regije. Upoređivan je oblik medijalne obrazne regije, kao i koordinate pet kefalometrijskih tačaka između genotipova oba gena, preoperativno, kao i 7 i 90 dana postoperativno. Rezultati. Preoperativno je nađena statistički visoko značajna razlika u obliku medijalne obrazne regije između wild type i mutanata PAX3 gena, dok statistički značajna razlika u obliku ispitivane regije nije nađena između wild type i heterozigota, kao ni između wild type u odnosu na heterozigote i mutante PAX3 gena, kao ni između genotipova TMTC2 gena. Sedam i 90 dana postoperativno, nije nađena statistički značajna razlika u obliku ispitivane regije između genotipova, kod oba gena. Zaključak. Polimorfizmi PAX3 i TMTC2 gena nisu povezani sa promenom morfologije lica nakon ekscizije tumora kože lica i zatvaranja defekta direktnom suturom.
Reference
Patemoster L, Zhurov AI, Toma AM, Kemp JP, St Pourcain B, Timpson NJ, et al. Genome-wide association study of three-dimensional facial morphology identifies a variant in PAX3 as-sociated with nasion position. Am J Hum Gen 2012; 90(3): 478–85.
Mabuchi F, Mabuchi N, Takamoto M, Sakurada Y, Yoneyama S, Kashiwagi K, et al. Japan Glaucoma Society Omics Group (JGS-OG). Genetic Variant Near PLXDC2 Influences the Risk of Primary Open-angle Glaucoma by Increasing Intraocu-lar Pressure in the Japanese Population. J Glaucoma 2017; 26(11): 963–6.
Madsen MB, Kogelman LJA, Kadarmideen HN, Rasmussen HB. Systems genetics analysis of pharmacogenomics variation dur-ing antidepressant treatment. Pharmacogenomics J 2018; 18(1): 144–52.
Runge CL, Indap A, Zhou Y, Kent JW Jr, King E, Erbe CB, et al. Association of TMTC2 With Human Nonsyndromic Sensori-neural Hearing Loss. JAMA Otolaryngol Head Neck Surg 2016; 142(9): 866–72.
Marenholz I, Esparza-Gordillo J, Rüschendorf F, Bauerfeind A, Strachan DP, Spycher BD, et al. Meta-analysis identifies seven susceptibility loci involved in the atopic march. Nat Commun 2015; 6: 8804.
Springelkamp H, Mishra A, Hysi PG, Gharahkhani P, Höhn R, Khor CC, et al. Meta-analysis of Genome-Wide Association Studies Identifies Novel Loci Associated With Optic isc Mor-phology. Genet Epidemiol 2015; 39(3): 207–16.
Meaike JD, Dickey RM, Killion E, Bartlett EL, Brown RH. Facial Skin Cancer Reconstruction. Semin Plast Surg 2016; 30(3): 108–21.
Kang SH, Kim MK, An SI, Lee JY. The effect of orthognathic surgery on the lip lines while smiling in skeletal class III pa-tients with facial asymmetry. Maxillofac Plast Reconstr Surg 2016; 38(1): 18.
Winkelbach S, Molkenstruck S, Wahl FM. Low-Cost Laser Range Scanner and Fast Surface Registration Approach. In: Franke K, Müller KR, Nickolay B, Schäfer R, editors. Pattern Recognition. Conference Proceedings; 28th DAGM Symposi-um; Berlin, Germany; 2006 September 12–14. Berlin, Heidel-berg: Sringer Verlag; 2006, p. 718–28.
Klingenberg CP. MorphoJ: an integrated software package for geometric morphometrics. Mol Ecol Resour 2011; 11(2): 353–7
Zalc A, Rattenbach R, Auradé F, Cadot B, Relaix F. Pax3 and Pax7 play essential safeguard functions against environmental stress-induced birth defects. Dev Cell 2015; 33(1): 56–66.
Goulding MD, Chalepakis G, Deutsch U, Erselius JR, Gruss P. Pax-3, a novel murine DNA binding protein expressed during early neurogenesis. EMBO J 1991; 10(5): 1135–47.
Macina RA, Barr FG, Galili N, Riethman HC. Genomic organi-zation of the human PAX3 gene: DNA sequence analysis of the region disrupted in alveolar rhabdomyosarcoma. Genomics 1995; 26(1): 1–8.
Lee AS, Yoon N, Gould M, Zhang M. Dynamic patterns of mononucleated myogenic cell populations in the developing rat hindlimb. Int J Dev Biol 2018; 62(4–5): 303–10.
Lee DH, Ahn SS, Kim JB, Lim Y, Lee YH, Shin SY. Down-regulation of α-Melanocyte-Stimulating Hormone-Induced Activation of the Pax3-MITF-Tyrosinase Axis by Sorghum Ethanolic Extract in B16F10 Melanoma Cells. Int J Mol Sci 2018; 19(6): pii: E1640.
Suzuki N, Mutai H, Miya F, Tsunoda T, Terashima H, Morimoto N, et al. A case report of reversible generalized seizures in a patient with Waardenburg syndrome associated with a novel nonsense mutation in the penultimate exon of SOX10. BMC Pediatr. 2018 May 23;18(1):171.
Singh AJ, Chang CN, Ma HY, Ramsey SA, Filtz TM, Kioussi C. FACS-Seq analysis of Pax3-derived cells identifies non-myogenic lineages in the embryonic forelimb. Sci Rep 2018; 8(1): 7670.
Russo I, Di Paolo V, Gurnari C, Mastronuzzi A, Del Bufalo F, Di Paolo PL, et all. Congenital Rhabdomyosarcoma: a different clinical presentation in two cases. BMC Pediatr 2018; 18(1): 166.
Hanna JA, Garcia MR, Lardennois A, Leavey PJ, Maglic D, Fagnan A, et al. PAX3-FOXO1 drives miR-486-5p and re-presses miR-221 contributing to pathogenesis of alveolar rhabdomyosarcoma. Oncogene 2018; 37(15): 1991–2007.
Burri M, Tromvoukis Y, Bopp D, Frigerio G, Noll M. Conserva-tion of the paired domain in metazoans and its structure in three isolated human genes. EMBO J 1989; 8(4): 1183–90.
Tachibana M, Takeda K, Nobukuni Y, Urabe K, Long J E, Meyers KA, et al. Ectopic expression of MITF, a gene for Waarden-burg syndrome type 2, converts fibroblasts to cells with mela-nocytes characteristics. Nat Genet 1996; 14(1): 50–4.
Sunryd JC, Cheon B, Graham JB, Giorda KM, Fissore RA, Hebert DN. TMTC1 and TMTC2 are novel endoplasmic reticulum tetratricopeptide repeat-containing adapter proteins involved in calcium homeostasis. J Biol Chem 2014; 289(23): 16085–99.
Bondurand N, Pingault V, Goerich DE, Lemort N, Sock E, Le Caignec C, et al. Interaction among SOX10, PAX3 and MITF, three genes altered in Waardenburg syndrome. Hum Molec Genet 2000; 9(13): 1907–17.
Tassabehji M, Read AP, Newton VE, Harris R, Balling R, Gruss P, et al. Waardenburg's syndrome patients have mutations in the human homologue of the Pax-3 paired box gene. Nature 1992; 355(6361): 635–6.
Tsukamoto K, Nakamura Y, Niikawa N. Isolation of two isoforms of the PAX3 gene transcripts and their tissue-specific alternative expression in human adult tissues. Hum Genet 1994; 93(3): 270–4.
Barber MC, Cloutier TE, Friedman TB. PAX3 gene structure, alternative splicing and evolution. Gene 1999; 237(2): 311–9.
Kim K, Heo DW, Kim S, Kim JS, Kim CS, Kang C. Expansive marker analysis replicating the association of glaucoma suscep-tibility with human chromosome loci 1q43 and 10p12.31. Eur J Hum Genet 2014; 22(3): 409–13.
Chen LJ, Tam PO, Leung DY, Fan AH, Zhang M, Tham CC, et al. SNP rs1533428 at 2p16.3 as a marker for late-onset prima-ry open-angle glaucoma. Mol Vis 2012; 18: 1629–39.
Cao D, Jiao X, Liu X, Hennis A, Leske MC, Nemesure B, et al. CDKN2B polymorphism is associated with primary open-angle glaucoma (POAG) in the Afro-Caribbean population of Barbados, West Indies. PLoS One 2012; 7(6): e39278.