Gender specific mRNA expression of HSPA8 in Parkinson’s disease

Abstract

HSPA8, is a molecular chaperone that plays a crucial role in assuring the protein quality. HSPA8, has therefore been hypothesized to be associated with Parkinson’s risk because the pathogenesis of this disease is characterized by intracellular protein misfolding and inclusion body formation. Also, epidemiological data suggest that the male gender is one of the risk factors for the development of PD. However, the molecular mechanisms underlying gender specificity in PD is less explored. Hence, we investigated the HSPA8 expression profile of male and female in a south Indian population and whether HSPA8 expression levels correlate with HSPA genetic variants and disease. Using quantitative real-time reverse transcription PCR (qRT-PCR) we quantified HSPA8 mRNA expression in peripheral blood lymphocytes (PBL) of thirty cases of Parkinson’s patients (PD) with anti-PD medications (20 males aged 65.85±1.19 and 10 females aged 65.7±1.202) and 30 age matched healthy people (20 males aged 68.45±1.282 and 10 females aged 65.8±1.133). Further, polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis was performed to detect gene variants in HSPA8. We observed that HSPA8 expression was markedly reduced in PD patients compared with control (p<0.05), but HSPA8 mRNA in males was reduced to greater degree (-48.56%) than in females (-38.28%). SSCP analysis detected polymorphisms at exon 4 of HSPA8, in both male and female patients, No significant difference in SSCP patterns were observed between genders of control and PD. On the molecular level, our results provide evidence that the expression profiles of HSPA8 of age matched normal and PD are gender specific. Altogether, we believe that our data provide a platform for investigating peripheral markers and understanding the role of gender in PD pathogenesis.

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