In a 9-year longitudinal study, we demonstrated that PDPARK16 variant carriers exhibited greater motor progression after 5 years of disease compared with non-carriers, suggesting that GWAS-linked gene variants may influence disease progression over time.
Within its limitations, this meta-analysis demonstrated that the rs823128 variants(G allele, GA and GG genotype)in PARK16 might be a potential protective factor for PD.
Our data does not support a strong direct interaction between LRRK2 and PARK16 variants; however, given the role of retromer and lysosomal pathways in PD, further studies are warranted.
However, the epidemiological evidence on the relationships between PARK16 single-nucleotide polymorphisms (rs823128, rs1572931, and rs823156) and PD is inconsistent.
PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead.
Sequence variants in SLC41A1 (solute carrier family 41 member 1) within the PARK16 locus have been reported to be associated with Parkinson's disease (PD).
Here we show that the consequences of variants at 2 such loci, PARK16 and LRRK2, are highly interrelated, both in terms of their broad impacts on human brain transcriptomes of unaffected carriers, and in terms of their associations with PD risk.
In a logistic regression analysis with SNPs coded under an additive model, there was no significant genetic interaction between the LRRK2 and the PARK16 locus gene RAB7L1 in PD risk.
Interestingly, gene SLC41A1 located in the novel PD locus PARK16 has recently been identified as being a Na⁺/Mg²⁺ exchanger (NME, Mg²⁺ efflux system), a key component of cellular magnesium homeostasis.
Herein, we investigated the effect of 4 single-nucleotide polymorphisms (SNPs) within the PARK16 locus, including rs823128, rs947211, rs823156, and rs11240572, on the risk of PD by genotyping 497 Taiwanese patients with PD and 500 age-matched control subjects.
The majority of studies have confirmed the association of the previously identified genetic risk factors, SNCA and MAPT, and two studies have identified three new PD susceptibility loci/genes (PARK16, BST1 and HLA-DRB5).
Using a dataset of post-mortem brain samples assayed for gene expression (n = 399) and methylation (n = 292), we identified methylation and expression changes associated with PD risk variants in PARK16/1q32, GPNMB/7p15, and STX1B/16p11 loci, hence suggesting potential molecular mechanisms and candidate genes at these risk loci.
There was a trend toward a stronger protective effect of SNPs at the PARK16 locus in sporadic PD compared to familial cases and in older compared to younger subjects.