Article,

Lack of association between COMT Val158Met and ZDHHC8 rs175174 polymorphisms and susceptibility to schizophrenia in a Brazilian population

.
Psychiatric Genetics, (2017)
DOI: 0.1097/YPG.0000000000000179

Abstract

The COMT Val158Met and ZDHHC8 rs175174 single-nucleotide polymorphisms (SNPs) have received increased attention in the molecular study of schizophrenia (SCZ) not only because they are localized to the main susceptibility locus of the disease, 22q11, but also because they are related to the dopaminergic status of the prefrontal cortex and the activity of several neuronal proteins, respectively (Karayiorgou and Gogos 2004; Shukla et al., 2016). Although several genetic association studies have obtained results suggesting a significant association of the COMT Val158Met and ZDHHC8 rs175174 SNPs with SCZ in terms of susceptibility, age at onset, or other clinical features, the role of these SNPs as markers of susceptibility for the disease is still controversial (Mukai et al., 2004; Sazci et al., 2004; Costas et al., 2011). In the present study, we evaluated the association between the COMT Val158Met and ZDHHC8 rs175174 SNPs and the susceptibility to SCZ through a case–control study involving a population from the North Region of Brazil. We used real-time PCR to genotype a total of 1094 participants: 544 unrelated patients (mean age: 40.18±12.59 years, 47.6% female), independently diagnosed by two experienced psychiatrists using the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th ed., and 550 healthy individuals (mean age: 40.04±12.26 years, 46.7% female), all of which were born in the state of Pará and whose ancestors were also born in the same state going back two previous generations. The research protocol was approved by the Ethics Committee of the Clinical Hospital Gaspar Viana. Statistical analysis was performed assuming four modes of inheritance: additive, dominant, recessive, and overdominant (Costas et al., 2011). Our study had a power of more than 75% in each SNP to detect an odds ratio (OR) of at least 1.4, assuming α is equal to 0.05 (http://biostat.mc.vanderbilt.edu/wiki/Main/PowerSampleSize). The genotype distributions were consistent with the Hardy–Weinberg equilibrium. Moreover, the haplotype analysis revealed a weak linkage disequilibrium (D’=0.020, r2=0.08) between the SNPs. The frequency of the COMT Met158 allele in all patients with SCZ was 35%, compared with 33% in the controls (OR=1.07; confidence interval 95%: 0.89–1.27; P=0.468). However, the frequency of the ZDHHC8 rs175174-G allele was 39% among patients with SCZ, whereas it was 35% among controls, which showed a marginally significant difference (OR=1.19; 95% confidence interval=1.00–1.4; P=0.054). However, the results of our analysis did not indicate any existing association between SCZ susceptibility and genotype distributions for both SNPs (P>0.05 in both crude and adjusted ORs), independent of the genetic inheritance model adopted. We also found that COMT Val158Met and ZDHHC8 rs175174 SNPs were not correlated with the sex of SCZ patients. Furthermore, no significant differences were observed for the mean age of onset of SCZ with respect to both SNPs, when analysed by one-way analysis of variance, Bonferroni post-hoc test, and Student’s t-test. Our results suggest that these SNPs do not play a major role in the pathogenesis of SCZ. However, the sample size for the current analyses was modest and replication is necessary.

Tags

Users

  • @silmarteixeira

Comments and Reviews