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Background  The transcription factor Nrf2, encoded by the  NFE2L2  gene, is an important regulator of the cellular protection against oxidative stress. Parkinson’s disease is a neurodegenerative disease highly associated with oxidative stress. In a previously published study, we reported associations of  NFE2L2  haplotypes with risk and age at onset of idiopathic Parkinson’s disease in a Swedish discovery material and a Polish replication material. Here, we have extended the replication study and performed meta-analyses including the Polish material and four new independent European patient-control materials. Furthermore, all SNPs included in the haplotype windows were investigated individually for associations with Parkinson’s disease in meta-analyses including all six materials.    Methods  Totally 1038 patients and 1600 control subjects were studied. Based on previous  NFE2L2  haplotype associations with Parkinson’s disease, five  NFE2L2  tag SNPs were genotyped by allelic discrimination and three functional  NFE2L2  promoter SNPs were genotyped by sequencing. The impact of individual SNPs and haplotypes on risk and age at onset of Parkinson’s disease were investigated in each material individually and in meta-analyses of the obtained results.    Results  Meta-analyses of  NFE2L2  haplotypes showed association of haplotype G AGC AAAA, including the fully functional promoter haplotype AGC, with decreased risk (OR = 0.8 per allele, p = 0.012) and delayed onset (+1.1 years per allele, p = 0.048) of Parkinson’s disease. These results support the previously observed protective effect of this haplotype in the first study. Further, meta-analyses of the SNPs included in the haplotypes revealed four  NFE2L2  SNPs associated with age at onset of Parkinson’s disease (rs7557529 G > A, −1.0 years per allele, p = 0.042; rs35652124 A > G, −1.1 years per allele, p = 0.045; rs2886161 A > G, −1.2 years per allele, p = 0.021; rs1806649 G > A, +1.2 years per allele, p = 0.029). One of these (rs35652124) is a functional SNP located in the  NFE2L2  promoter. No individual SNP was associated with risk of Parkinson’s disease.    Conclusion  Our results support the hypothesis that variation in the  NFE2L2  gene, encoding a central protein in the cellular protection against oxidative stress, may contribute to the pathogenesis of Parkinson’s disease. Functional studies are now needed to explore these results further.    Electronic supplementary material  The online version of this article (doi:10.1186/s12881-014-0131-4) contains supplementary material, which is available to authorized users.

Genetic associations of Nrf2-encoding NFE2L2 variants with Parkinson’s disease – a multicenter study