Objective: Human endogenous retroviruses (HERVs) and associated sequences occupy ~8% of the human genome and dysregulation of HERV transcripts may have significant impacts on human health including psychiatric disorders. HERV-K18 is still active in the human genome and its envelope gene encodes a superantigen (SAg) which may result in deregulation of the immune system. In the study, the possible associations of the two variants localized in the SAg-coding region of HERV-K18 with bipolar disorder type I (BD-I) were evaluated.
Methods: The subjects included 100 patients with BD-I and 100 age- and sex-matched healthy controls. The effects of the two HERV-K18 variants (HERV-8594 and HERV-8914) were analyzed with Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. The possible associations of the genotypes/alleles in BD-I patients with several clinical and demographic data were also evaluated.
Results: HERV-8914 TT genotype had approximately 5.36 times higher risk of BD-I than those with the CC genotype (OR=5.386, 95% CI=1.602-18.11). Moreover, the prevalence of the CC genotype in patients with hypomania (31.25%) was found to be higher than that observed in patients without hypomania (10.71%) (Fisher’s Exact test= 5.931, p=0.036).
Conclusion: This is the first study implying that HERV-K18 variations may be associated with the pathogenesis of BD-I.