The transcription factor Pitx3 is a risk modifier for Parkinson’s disease in a Chinese Han population

Background and purpose: The transcription factor Pitx3 plays a crucial role in the development and survival of midbrain dopaminergic (mDA) neurons, especially the mDA neurons in the substantia nigra pars compacta. The degeneration of these neurons is the pathological hallmark in Parkinson’s disease (PD). Several polymorphisms of the Pitx3 gene have been linked with sporadic and early-onset forms of PD, but different studies have given conflicting or inconsistent findings. Amongst the polymorphisms studied, the single-nucleotide polymorphism (SNP) rs3758549, located in the promoter region of Pitx3 gene, is one of the most well-studied but also one of the most controversial. In order to explore the nature of this association in greater detail and in a new ethnic group, we carried out a case–control study of the SNP rs3758549.

Methods: A total of 316 patients with sporadic PD and 305 healthy controls, from two centers in mainland China, were analyzed in our study. The genotypes at rs3758549 were determined by PCR-restriction fragment length polymorphism analysis. And we also analyzed the association between genotype and phenotype.

Result: Our data showed a significant association between the rs3758549 polymorphism and PD (P = 0.012, OR = 1.50, 95%CI: 1.15–1.96). Furthermore, allele T of SNP rs3758549 was significantly more frequent in early-onset PD than in healthy controls (P < 0.001).

Conclusion: Our findings indicate that the SNP rs3758549 (C > T substitution) in the Pitx3 gene is a potential risk for sporadic PD, especially early-onset PD in Chinese Han population.