Brief Association Letters
Internalizing disorders include common mood and anxiety disorders and constitute a major public health concern (Krueger and Markon, 2006). Little research has been conducted on the association between the serotonin transporter (5-HTT or SLC6A4) gene and internalizing disorders. To our knowledge, no results have been reported on the relationship between the coding region of SLC6A4 and internalizing disorders. In this study we explored whether single-nucleotide polymorphisms (SNPs) on the coding region of the SLC6A4 gene increase the risk of developing internalizing disorders in a young adult Chinese population.
This was a case–control study. The 259 cases and 269 matched controls were a subset of a larger survey on the mental health of Chinese university students. The WHO Composite International Diagnostic Interview Version 3.0 (CIDI-3.0) was used as the diagnostic tool. The HaploView 4.1 (Barrett et al., 2005) was used to select tag SNPs on the coding region of SLC6A4. Six tag SNPs (rs3794808, rs6354, rs11080122, rs2020942, rs2020939, and rs12449783) were selected and genotyped using PCR-ligase detection reaction (Liu et al., 2009).
There were no significant statistical differences in the distributions of age, sex, grade, and study program between case and control groups (P>0.05). The Hardy–Weinberg equilibrium was not rejected in any of the selected tag SNPs in either group (P>0.05). The genotypic frequencies of the six tag SNPs in cases/controls were as follows: rs12449783 – AA (0.04/0.05), AC (0.35/0.35), CC (0.61/0.60); rs3794808 – GG (0.04/0.04), AG(0.28/0.31), AA (0.68/0.64); rs2020942 – GG (0.81/0.80), AG (0.17/0.19), AA (0.02/0.01); rs11080122 – CC (0.80/0.80), CT (0.19/0.20), TT (0.01/0.00); rs6354 – AA (0.76/0.79), AC (0.22/0.21), CC (0.02/0.00); and rs2020939 – CC (0.07/0.08), CT (0.43/0.39), TT (0.50/0.52). None of selected SNPs were significantly associated with internalizing disorders (all P>0.05). Both dominant and recessive models showed no association between the SNP genotypes and the risk of internalizing disorders (P>0.05). No haplotypic association was observed in the SLC6A4 gene (P>0.05). Our findings are consistent with two studies on the relationship between 5-HTTLPR and internalizing disorders (Young et al., 2003; Benjet et al., 2010). It would appear that there are no significant associations between the SLC6A4 gene and internalizing disorders. These negative findings could be explained by: (a) the heterogeneity in internalizing disorder phenotypes; (b) the fact that these polymorphisms on SLC6A4 contribute a modest effect but do not have a major role in the onset of psychiatric disorders; and (c) the presence of other components (genetic and environmental factors) interacting with the SLC6A4 gene.
Future research should be conducted to attempt to replicate our findings in a larger study sample and with other ethnic populations. 5-HTTLPR should also be added as a candidate polymorphism to explore its individual and joint influence with other polymorphisms located on the coding region of SLC6A4 in internalizing disorders.
The authors thank the undergraduates for their participation. This work was supported by a grant from the National Natural Science Foundation of China (Grant No. 30972536). As Postdoctoral Fellows X.M. is sponsored by Saskatchewan Health Research Foundation (SHRF), and C.K. was sponsored by SHRF.
Conflicts of interest
There are no conflicts of interest.
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