Gene‐Gene Interaction Between FGF20 and MAOB in Parkinson Disease

Abstract

SummaryThe fibroblast growth factor 20 (FGF20) and monoamine oxidase B (MAOB) genes are associated with Parkinson Disease (PD) risk and both are in the dopamine bio-pathway. Therefore, we investigated the joint effect between polymorphisms in the FGF20 and MAOB genes for evidence of interaction contributing to PD risk. Fourteen polymorphisms (eight for FGF20, six for MAOB) were genotyped in 736 families and analyzed using conditional logistic regression (CLR). Significant two-locus interactions were found in females between the polymorphisms rs1721100 of FGF20 and rs1799836 of MAOB, and between the polymorphisms rs1721082 of FGF20 and rs1799836 of MAOB. The risk alleles for each SNP identified from CLR, rs1721100 C, rs1721082 T and rs1799836 A, are consistent with previous reports. Using indicator variables for the SNP genotypes, rs1721100 GC with rs1799836 AA showed significant interaction (P = 0.021), compared with the reference group rs1721100 GG with rs1799836 GG. Using an allele-dose model for the risk alleles, rs1721100 and rs1799836 showed significant interaction (P = 0.019). We found similar interaction results between rs1721082 and rs1799836. In conclusion, variants in FGF20 and MAOB show evidence of statistical interactions, which emphasizes the importance of considering them jointly in genetic analysis of PD and illustrates potential patterns of biological interaction contributing to PD risk.

Polygenic determinants of Parkinson's disease in a Chinese population

“…The effects of individual SNPs may be with limited value in predicting risks, and combining multiple low-penetrance SNPs may have stronger predictive power. There have been a few studies on the gene-gene interaction in affecting risk for PD, such as SNCA and MAPT gene, SNCA, MAPT and GSK3B, and FGF20 and MAOB Gao et al, 2008;Trotta et al, 2012;Wider et al, 2011), but little positive effects have been found. Our present study is the first comprehensive study paying attention on independent and joint effects of the variants within SNCA, LRRK2, GBA, MAPT, PARK16, GAK, HLA-DR, and BST1 genes or loci in PD in an ethnically homogeneous Chinese population.…”

“…Genetic variations may be susceptibility factors or disease modifiers, affecting penetrance, age at onset, severity, and progression . Studies have examined the possibility that gene-gene interactions might account for part of a disease risk Gao et al, 2008;Trotta et al, 2012;Wider et al, 2011); however, the population-attributable risk remains limited, and more genetic factors are to be identified. In this study, we performed a comprehensive analysis of 16 SNPs from 8 candidate genes or loci mainly with Sanger sequencing that could also be substituted by more applicable methods such as just recently published NeuroX array and so on (Nalls et al, 2014).…”

“…Whether combinations of individual variants will confer larger more clinically useful associations with increased risk remain to be shown. Until now, there are only a few studies reporting about the gene-gene interaction on susceptibility to PD, such as the interaction of SNCA and MAPT gene; SNCA, MAPT, and GSK3B; and FGF20 and MAOB Gao et al, 2008;Trotta et al, 2012;Wider et al, 2011).…”

Chromosome 8p as a potential hub for developmental neuropsychiatric disorders: implications for schizophrenia, autism and cancer

“…353,354 Moreover, FGF20 at 8p21.3-22 was identified as a risk factor for Parkinson's disease. [161][162][163][164] Likewise, Murase & McKay 168 showed, in vitro experiments, that FGF signals (specifically, FGF20 and FGFR1) to elevate dopamine levels and protect the specific midbrain neuron type. Because Parkinson's disease is characterized by loss of midbrain dopaminergic neurons, it is possible that altered FGF-signaling might have permanent effects on CNS function by the dopaminergic nigrostriatal system.…”

The FGF Family in Humans, Mice, and Zebrafish: Development, Physiology, and Pathophysiology

“…Parkinson disease (PD) is caused by a pathogenic process responsible for the loss of dopaminergic neurons within the substantia nigra pars compacta. A pedigree disequilibrium test and a case-control association study indicated that Fgf20 is potentially a risk factor for PD (Gao et al, 2008).…”