VARIANTS IN MITOCHONDRIAL tRNA GENE MAY NOT BE ASSOCIATED WITH THYROID CARCINOMA
Lv F1,a, Qian G2,a, You W1,a, Lin H3, Wang XF3, Qiu GS2, Jiang YS2, Pang LX3, Kang YM4, Jia BF4, Xu JZ5,*, Yu Y1,*
*Corresponding Author: Dr. Jinzhong Xu, Department of Clinical Pharmacy, the Affiliated Wenling Hospital of Wenzhou Medial University, Taiping Nan Road 190, Wenling 317500, People’s Republic of China. Tel./Fax: +86-(0)576-8620-6288. E-mail: xujzwl@163.com and Dr. Yang Yu, Department of Breast Surgery, Henan Provincial People’s Hospital, Weiwu Road 7, Zhengzhou 450003, People’s Republic of China. Tel./Fax: +86-(0)371- 6558-0014. E-mail: 510790135@qq.com
page: 59

RESULTS

Study Characteristics. As a result, three studies were identified using the keywords mentioned in the previous section. After a full-text review, we noticed that one of them concerned the somatic mtDNA mutations in PTC [12]. Another article that met our inclusion criteria was about the association of mtDNA transversion mutations with familiar MTC [13], whereas another article talked mainly about the mtDNA mutations causing defective OXPHOS in thyroid carcinoma [14]. Selecting Thyroid Carcinoma Associated mttRNA Variants. We further screened the mt-tRNA variants that had been reported with thyroid cancer. Consequently, a total of seven mt-tRNA variants were described: tRNAAsp G7521A, tRNAArg T10411C and T10463C, tRNALeu(CUN) A12308G, tRNAIle G4292C and C4312T, and tRNAAla T5655C. The molecular characterization of these mt-tRNA variants are listed in Table 1 and Figure 1. Conservation Assessment of These Variants. Assessing pathogenicity of a nt substitution in a mttRNA gene involved evaluation of the evolutionary conservation of the base involved. For this purpose, we analyzed the CIs of these mt-tRNA variants. Briefly, we chose 15 animals for inter-species analysis, these species included Mus musculus, Gorilla gorilla, Hylobates lar, Lemur catta, Pan paniscus, Homo sapiens, Thylamys elegans, Procavia capensis, Cavia porcellus, Orycteropus afer, Bos taurus, Sus scrofa, Felis catus, Platanista minor and Herpestes javanicus. We used the sequences derived from mammalian mitochondrial tRNA genes (http://mamit-trna.u strasbg.fr/) [15]. The CI was calculated by comparing the corresponding nt at the position of mt-tRNA. We found that the T10463C, A12308G and T5655C variants exhibited the highest level of CI, whereas other mutations lacked high level of CIs. Notably, the CI of the A12308G mutation is 93.3% (Figure 2). Prediction of the ⊿G of Each mt-tRNA. We used the RNA Fold Web Server (http://rna.tbi.univie. ac.at/cgi-bin/ RNAfold. cgi) to calculate the ⊿G of each mt-tRNA with and without these mutations, as listed in Table 1. Surprisingly, none of these variants caused significant alternation of ⊿G between the wildtype and the mutant mt-tRNAs, it seemed that they may not play important roles in thyroid carcinoma. Mutational Analysis of the tRNALeu(CUN) Gene. By comparing the human mitochondrial genome sequence, we found that there were five thyroid cancer patients and three control subjects carrying the homoplasmic A12308G variant, suggesting that it may be very polymorphic in the human population.



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