Parkinson's disease (PD) is a common neurodegenerative disorder with multiple factors contributing to disease pathogenesis. Previous studies implicated the involvement of the transcription factor hypoxia inducible factor 1 alpha (HIF1A) in PD through its transcriptional regulation of PD-associated genes. This study uses molecular inversion probes (MIPs) followed by high-throughput sequencing for the genetic analysis of HIF1A in a large cohort including 1692 ethnic Han Chinese PD patients and 1419 neurologically normal control subjects matched for age, gender, and ethnicity. Common HIF1A variant rs11549465 was found to be associated with increased late-onset PD (LOPD) risk (OR (95%CI) = 1.531(1.068-2.194), P = 0.03828 for trend test, P = 0.03948 for analyses using the allelic model and P = 0.04196 for logistic regression analyses (sex + age as covariates)). Though the gene-based variants burden test is negative, seven rare non-synonymous, predicted-pathogenic point variants were identified. In conclusion, our study further indicates that HIF1A plays a role in PD pathogenesis.
Keywords: HIF1A; Molecular inversion probes; Parkinson’s disease; rs11549465.