The availabilities of serotonin and dopamine are modulated b
The availabilities of serotonin and dopamine are modulated by the serotonin transporter and catechol-O-methyltransferase enzyme. The serotonin transporter (5-HTT) is a key protein that reuptakes serotonin from the synaptic cleft back into synaptic boutons (Coleman et al., 2016; Talvenheimo et al., 1979). Meanwhile, the functions of 5-HTT is determined by the serotonin transporter gene-linked polymorphic region (5-HTTLPR). The short allele (S) of 5-HTTLPR, as compared with the long allele (L), is related to lower ratio of serotonin recycling (Canli and Lesch, 2007). Additionally, the functions of 5-HTT are also modulated by the rs25531 polymorphism. The G allele of rs25531 is always in phase with the L allele of 5-HTTLPR, and the SS/SA and SALG haplotypes are related to lower 5-HTT expression as compared with the LALA haplotype (Kosek et al., 2009). The catechol-O-methyltransferase (COMT) enzyme is a critical enzyme for degrading dopamine (Liang et al., 2017; Weinshilboum, 1988). Within the COMT gene, a functional polymorphism in codon 158 (Val158Met), leading to an amino cetylpyridinium substitution of valine (Val) for methionine (Met), leads to the Met/Met genotype showing 40% less enzymatic activity than the Val/Val genotype (Bilder et al., 2004; J. Chen et al., 2004; Lachman et al., 1996). So far, studies indicated that the two functional polymorphisms are related to emotional processing (Fisher et al., 2015; Montag et al., 2008; Viddal et al., 2017; Williams et al., 2010) and depressive symptoms (Gong et al., 2017; Karg et al., 2011). Therefore, we examined the associations of 5-HTTLPR and COMT Val158Met polymorphisms with alexithymia. Ten studies have examined the associations of 5-HTTLPR and COMT Val158Met polymorphisms with alexithymia. Among them, five studies investigated the roles of 5-HTTLPR (Ham et al., 2005; Kano et al., 2012; Mandelli et al., 2013; Porcelli et al., 2015; Terock et al., 2018), and other five studies examined the roles of COMT Val158Met (Ham et al., 2005; Hermes et al., 2011; Koh et al., 2016; M. Swart et al., 2011; Zekioglu et al., 2014). However, the findings were inconsistent given the small sample sizes and population stratifications of previous studies. For the 5-HTTLPR polymorphism, three studies (N = 304, 61, 130) showed that the L/L genotype was related to higher score on alexithymia as compared with the L/S or S/S genotype (Kano et al., 2012; Mandelli et al., 2013; Porcelli et al., 2015), one study (N = 5283) showed that the L allele was related to low score on alexithymia (Terock et al., 2018), while an early study failed to detect any correlation at all (Ham et al., 2005). For the COMT Val158Met, two studies (N = 109, 244) showed that the Val/Val genotype was related to higher levels of alexithymia than the Met/Met or Met/Val genotype (Ham et al., 2005; Koh et al., 2016), and one study (N = 40) showed that the Met/Met or Met/Val genotypes was related to less difficulty in verbalizing their feelings than the Met homozygotes (Swart et al., 2011), while the other two studies (N = 240, 157) showed no correlation at all (Hermes et al., 2011; Zekioglu et al., 2014). Given the mixed findings, it was necessary for us to investigate the associations with a larger population and to carry out meta-analyses basing on the previous studies. Overview, to address the associations of 5-HTTLPR and COMT Val158Met with alexithymia, we conducted two studies. In the study 1, we replicated the associations of 5-HTTLPR and COMT Val158Met with alexithymia in a large population (N = 1698). Given the interactions between 5-HTTLPR and COMT Val158Met on brain functions of emotional processing (Radua et al., 2014; Surguladze et al., 2012), we also examined interactions of the two polymorphisms on alexithymia. Moreover, given that two previous studies indicated a significant difference in the score of alexithymia between the L carriers and SS genotype groups (Porcelli et al., 2015; Terock et al., 2018) and one study demonstrated a significant difference between the LL genotype group and S carriers (Kano et al., 2012), we were also examined the genetic effects with different genetic effect models: Recessive, dominant, and co-dominant genetic effect models (Thakkinstian et al., 2004; Thakkinstian et al., 2005). In the study 2, we re-examined the associations with meta-analyses by pooling the current data with previous findings.