Sex-specific Relationships between the rs371194629 Polymorphism of the HLA-G Gene, Cognitive Impairments, Autistic Traits, and Social Functioning in Schizophrenia

Background: the expression alteration of the HLA-G gene encoding the human leukocyte antigen G presumably impairs embryonic development and thus increases schizophrenia risk. Prior studies found the associations of the HLA-G rs371194629 (14bp INDEL) polymorphism with the disease risk and social functioning of patients. This work continued to explore the contribution of the rs371194629 polymorphism to key schizophrenia syndromes, presumably reflecting neurodevelopmental disorders.

The aim was to assess the association of cognitive deficits and autistic traits with the rs371194629 polymorphism and the role of these phenotypes as mediators of the relationship between rs371194629 and social functioning in schizophrenia patients.

Patients, Participants and Methods: the sample included 555 psychotic patients with schizophrenia spectrum disorders and 261 healthy subjects who underwent cognitive testing. In addition, the PAUSS as measure of autism trait severity was calculated for patients. Covariance analysis and structural equation modeling were applied to assess the association of cognition and autistic traits with rs371194629 and the potential role of these syndromes as mediators between genotype and social functioning measured with the Personal and Social Performance Scale.

Results: the analysis revealed a nominally significant association of the DelDel genotype with reduced cognitive functioning in schizophrenia male patients (p = 0,022). The rs371194629 polymorphism was not associated with the severity of autistic traits. The cognitive deficits and autistic traits were not mediators of the rs371194629 effects on social functioning.

Conclusions: the results suggest the contribution of the HLA-G gene polymorphism to the severity of cognitive impairment in schizophrenia and are consistent with prior data that revealed the sex-dependent association of rs371194629 with schizophrenia and the relationship of the DelDel genotype with a less favorable disease course in the Russian population. 

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