Polymorphism analysis of HOPA: A candidate gene for schizophrenia

Abstract

HOPA is a 25 kb Xq13 gene that codes for a member of the thyroid receptor co-activator protein (TRAP) family of nuclear receptor co-activators. In our prior research, polymorphisms in the opposite paired (Opa) domain of HOPA have been associated with a syndrome of aberrant behavior, most prominently psychosis, and hypothyroidism. These Opa domain polymorphisms are intriguing because subsequent research has demonstrated that changes in the Opa domain of the C. elegans orthologue of HOPA results in altered neurogenesis and release of transcriptional suppression. In an effort to determine whether other allelic polymorphisms in this gene exist and may potentially contribute to increased susceptibility to neuropsychiatric illness, we have performed single stranded conformational polymorphism (SSCP) analysis of all 45 exons and each of the two potential promoter regions of HOPA using DNA from a panel of patients with psychosis. We found a rare promoter polymorphism in an individual with schizoaffective disorder and extremely low thyroid stimulating hormone (TSH). The most common exonic polymorphism in HOPA is the previously demonstrated HOPA(12 bp) polymorphism. Transmission disequilibrium analysis of the HOPA(12 bp) polymorphism showed segregation with affected status in six of eight instances. We suggest that this evidence supports previous associations of HOPA(12 bp) with a broad range of neuropsychiatric illness and conclude that further studies of this uncommon polymorphism are merited.

A meta-analysis of the association of the HOPA12bp polymorphism and schizophrenia

“…Fourth, it should be noted that the HOPA 12bp polymorphism itself is in linkage disequilibrium with a substantial haplotype on Xq13. Therefore, even if the current analyses are correct, it is possible that the HOPA 12bp polymorphism may not be responsible for some or all the effects associated with this haplotype, although the results of Sandhu et al (2003) make this possibility less likely. Fifth and finally, secondary to the low number of observations of the HOPA 12bp allele, the As an overlapping control group was used in the DeLisi and Philibert studies, the result of these two studies were pooled for this analysis with the resulting joint odds ratio being reported on the line for the Philibert et al study.…”

“…Two studies (Kirov et al, 2003;Sandhu et al, 2003) examined the relationship of the HOPA 12bp allele by transmission disequilibrium testing (TDT) using trios informative for an X-chromosome loci (i.e. using only the mothers of probands as fathers of probands only have one X-chromosome).…”

JMJD6 Licenses ERα-Dependent Enhancer and Coding Gene Activation by Modulating the Recruitment of the CARM1/MED12 Co-activator Complex

“…It has been shown that med12 gene is essential for early development in mouse and is involved in the transcriptional regulation of many signaling pathways (Philibert and Madan, 2007, Rocha et al, 2010). MED12 has been shown to be implicated in a number of neurological disorders (Xu et al, 2011, Philibert and Madan, 2007, Sandhu et al, 2003, Graham and Schwartz, 2013, Risheg et al, 2007, Schwartz et al, 2007, Ding et al, 2008) as well as human cancers (Schiano et al, 2014, Turunen et al, 2014, Huang et al, Shalem et al, 2014, Wang et al, 2015). Particularly, MED12 was linked to drug resistance in multiple cancer types including breast, colon, lung cancers and melanoma (Wang et al, 2015, Shalem et al, 2014, Huang et al, 2012).…”

The Sex Chromosome Hypothesis of Schizophrenia: Alive, Dead, or Forgotten? A Commentary and Review

“…Also codes proteins critical in the regulation of transcription via the Wnt and receptor tyrosine kinase pathways, both of which are involved in cell differentiation and growth [70].…”