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  • The COMT gene is involved in numerous psychological and


    The COMT gene is involved in numerous psychological and physiologic processes, including modulation of pain. Polymorphisms in this gene have also been associated with many painful conditions, including pain sensitivity in children. Bivariate analysis demonstrated that individuals with heterozygous CG for rs4818 (allele G being the predisposing one) had a 4.71 higher risk of BMG. This suggests that COMT is more likely to be an associating factor rather than the etiologic factor for BMG. The evaluated polymorphism rs4818 is a synonymous alteration, in which the Fmoc-Tyr(tBu)-OH change also results in a leucine. This may explain the lack of association in the multivariate regression adjusted by HAM-A scores. The 5HTT polymorphisms rs3813034 G/A and rs1042173 G/T were associated with BMG. In fact, individuals with rs3813034, homozygous C, and rs1042173, homozygous T, had 2.87 and 3.42 higher risks, respectively, for BMG, independent of anxiety level. This suggests that the presence of these genotypes increase the risk of BMG. Not surprisingly, genetic polymorphisms in the 5HTT gene have been associated with a variety of conditions, including pain perception and regulation,21, 33 pediatric migraine, and monthly headaches caused by overuse of medications. To our knowledge, this is the first study to demonstrate an association between polymorphisms in the 5HTT gene and BMG.39, 40 These polymorphisms are probably related to gene expression regulation, as well as microRNA regulation. Also, antidepressant drugs are known to be downregulated by 5HTT,38, 41 so it is quite possible that in the future, antidepressant drugs could be efficacious in the treatment of symptomatic BMG. As yet, there is no evidence for such a treatment in the literature. It is important to highlight the fact that when we used the anxiety-adjusted genetic model in our study, the values of association were similar to the univariate results. This emphasizes the importance of the 2 factors analyzed—anxiety and genetic polymorphisms—in the occurrence of BMG. It is possible to view these factors in the conceptual framework (Figure 1). It was, however, not possible to define what comes first—anxiety or genetic polymorphism—because of the design of our study, which was cross-sectional, not a cohort, study. Further studies should be performed to elucidate this relationship. Putting our findings together with those reported in the current literature on BMG, the theory by Redman et al. was reinforced. Redman et al. suggested a polygenic model of hereditary transmission, with a threshold for susceptibility to environmental factors, as the best model of explanation for the development of BMG. In summary, our results support the hypothesis that anxiety and the polymorphisms rs3813034 and rs1042173 in the 5HTT gene are associated with BMG and could be markers for this condition.
    Conclusions Anxiety increases the risk of BMG, independent of genotypes. Alterations in the genotypes were associated with BMG, in which individuals who carry the TT genotype in rs1042173, as well as the CC genotype in rs3813034 in 5HTT, had a higher risk for BMG.
    Introduction The cytochrome p450 family 2, subfamily D, polypeptide 6 (CYP2D6) enzyme is responsible for phase I metabolism of approximately 30% of marketed drugs and endogenous toxins [1], [2]. CYP2D6 is a highly variable pharmacogene with well documented allele distributions that vary by demography [3], [4], [5], [6]. Constellations of individual single nucleotide (SNPs) or insertion/deletion (INDELs) polymorphisms in CYP2D6 define star (*) alleles (i.e. a haplotype [operationally defined by a set of SNPs]) which may be used to predict the metabolizer phenotype (e.g. poor [PM], intermediate [IM], extensive/normal [EM/NM] and ultrarapid [UM]) of an individual using their CYP2D6 diplotype (i.e., combination of two CYP2D6 * alleles) information and associated activity scores. These data have demonstrated value for guiding individualized prescription medication practices and even post-mortem investigations [7], [8], [9], [10].