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  • br Discussion br The present study evaluated the potential r

    2020-03-17


    4. Discussion
    The present study evaluated the potential role of the DIO1 and DIO2 gene polymorphisms in thyroid cancer disease as well as in explaining the differences in thyroxin dose requirement by patients undergoing treatment for differentiated thyroid cancer. In all, we elected to investigate one DIO1 and three DIO2 variants. None of these SNPs showed any association with the disease. To date, while polymorphisms of deiodinases have been described for some malignancies and several other forms of the diseases, information on their possible involvement in thyroid cancer remains scanty. Specifically, the DIO2 gene has been associated with diseases such autoimmune hypothyroidism disease (Carle et al., 2017), maternal thyroid status (He et al., 2009), grave’s dis-ease (Inoue et al., 2018), drinking behavior (Lee et al., 2015), cogni-tive impairment (Luo et al., 2015), osteoarthritis (Waarsing et al., 2011; Meulenbelt et al., 2008), but not with thyroid cancer. On the other hand, it is widely acknowledged that, since serum TSH is a sensitive indicator of thyroid function, overt abnormalities in
    TGA
    Fig. 1. The figure represents a schematic diagram of the DIO1 (not to scale) showing the SNPs studied and their chromosomal loci.
    Please cite this article as: M. M. AlRasheed, A. AlAnzi, R. AlShalhoub et al., A study of the role of DIO1 and DIO2 polymorphism in thyroid cancer and drug response to therapy in the Saudi population, Saudi Pharmaceutical Journal, https://doi.org/10.1016/j.jsps.2019.05.005
    4 M.M. AlRasheed et al. / Saudi Pharmaceutical Journal xxx (xxxx) xxx
    Promoter 
    ATG
    Fig. 2. The figure represents a schematic diagram of the DIO2-210 transcript (not to scale) showing chromosomal loci of studied SNPs.
    Table 2
    Association of DIO1 and DIO2 variants with differentiated thyroid cancer risk.
    Gene SNP ID Genotypes Patients f(%) Control f(%) P OR(95%CI)
    The table compares the real-time PCR data for the 507 studied DTC patients versus 560 healthy controls. SNP ID gives the single nucleotide identification number denoted with the ‘‘rs” nomenclature. f(%) gives the frequencies of the genotypes of Necrosulfonamide as a percentage. The letters A, C, G and T are the codes for the nucleotides adenine, cytosine, guanine and thymine respectively. OR, odds ratio; CI, confidence Interval; NS, non-significant; P, P value. Each SNP was entered in a multivariate analysis including age, sex, and smoking.
    this function lead to common endocrine disorders affecting a size-able number of individuals over a life span. These malfunctions are likely to underlie genetic defects. Of the SNPs discussed herein, the rs2294512_A > G of the DIO1 gene has been found to interact with serum selenium in Crohn patients (Gentschew et al., 2012) and reduced psychological well-being in hypothyroid patients (Young Cho et al., 2017), while the rs1388378_G > T has been linked to mental retardation in the Chinese population (Zhang et al., 2012). Hence, although we were not able to establish any positive rela-tionship for the SNPs with disease per se, genetic alterations in
    Table 3
    Demographics data of individuals involved in the thyroxine dose association study.
    All Male
    Female
    N, number of individuals in the group; BMI, body mass index; TSH, thyroid stim-ulating hormone; FT4, free thyroxine level; L-T4; Dose is given as mg/kg.
    the TSH pathways are likely to play an important role in thyroid cancer manifestation.
    One important subject of interest of the present study was the likelihood that changes in the DIOs may explain why DTC patients tend to respond in various fashions to the therapy with thyroid hormones, with some patients requiring thyroxine dose adjust-ments. When we looked at the cases as a whole, we were able to link these differences to rs1388378_G > T. However, when patients were classified as being in either the near-suppressed or in the suppressed group, this variant lost its link with dose requirement in ether category. Like in the disease manifestation, there is cur-rently lack of information on the role of the DIOs in differential response to hormonal therapy of thyroid cancer. On the other hand, the observation that D2 metabolizes T4 into T3 and reverse rT3 into T2, while D1 functions as a scavenger by removing iodo groups means that functional changes in either of the encoding genes is likely to trigger perturbations in the hormone metabolism. To date the genes have been linked to TSH suppression (Santoro et al., 2014), shift in pattern of secretion of thyroid hormone (Peltsverger et al., 2012) and TRH-mediated acute rise in TSH (Luo et al., 2015). Among the variants discussed in the present paper, the rs12885300 is perhaps the most well-studied. It has been linked to TSH suppression (Santoro et al., 2014), TRH-