The role of G196A polymorphism in the brain-derived neurotrophic factor gene in the cause of Parkinson’s disease: a meta-analysis

Abstract

The association between Parkinson's disease (PD) and the G196A polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been investigated in several case-control studies, producing contradictory results: one study indicated that homozygocity of AA is associated with PD, another study produced the opposite result, whereas other studies found no association. To investigate these contradictory findings, a metaanalysis of all available association studies between the G196A polymorphism and the risk of developing PD was conducted. Four out of six identified studies included populations of East Asian descent, and two included populations of European descent (Whites). Overall, the meta-analysis of the allele contrast (A vs G) suggested large heterogeneity between studies (P=0.07, I 2 =51%) and no association between G196A and the risk of developing PD: random effects odds ratio (OR)=1.00 [95% CI (0.85, 1.18)]. The sensitivity analysis (exclusion of two studies: one East Asian and one White) with the controls not in Hardy-Weinberg equilibrium showed large heterogeneity (P=0.10, I 2 =52%) and no significant association: random effects OR=0.94 [95% CI (0.77, 1.15)]. The subgroup analyses for East Asians and Whites produced no significant association. In addition, the contrast of homozygotes, and the dominant and recessive models for allele A did not support a major role for this polymorphism in the pathogenesis of PD. There were no sources of bias in the selected studies, and the differential magnitude of effect in large vs small studies was not significant. The metaanalysis results suggest that the involvement of the BDNF gene in susceptibility to PD merits further exploration with larger and more rigorous population association studies.

Do alcohol-metabolizing enzyme gene polymorphisms increase the risk of alcoholism and alcoholic liver disease?

“…Only studies that used validated genotyping methods were considered, and the distribution of the genotypes in the control group was tested for Hardy-Weinberg equilibrium (HWE) (P Ն .05). [16][17][18] Finally, studies based on pedigree data were excluded because they investigate linkage and not association. 19 Data Abstraction.…”

“…The pooled OR was estimated using fixed effect (FE) (Mantel-Haenszel) and random effect (RE) (DerSimonian and Laird) models. 17 Random effects modeling assumes a genuine diversity in the results of various studies and incorporates to the calculations a between study variance. Therefore, when there was heterogeneity between studies, the pooled OR was estimated using the RE model.…”

“…Studies with controls not in HWE were subjected to a sensitivity analysis. 17,18 In sensitivity analysis, the effect of excluding specific studies was examined. Analyses were performed using Meta-Analyst (Lau, Boston, MA), and CVF90.…”

Association of methylenetetrahydrofolate reductase (MTHFR) polymorphisms with genetic susceptibility to gastric cancer: a meta-analysis

“…However, the consistency of genetic effects across these traditionally defined racial groups does not necessarily mean that race-specific genetic effects are exactly the same. Analyses were performed using Meta-Analyst (Joseph Lau, Boston, Massachusetts, USA 1998), and CVF90 with IMLS library (Zintzaras and Hadjigeorgiou 2005;.…”

Folate Pathway Gene MTHFR C677T Polymorphism and Risk of Lung Cancer in Asian Populations

“…Heterogeneity was quantified with the I 2 metric (I 2 =(Q-df)/Q), which is independent of the number of studies in the meta-analysis. I 2 takes values of between 0 and 100%, with higher values denoting a greater degree of heterogeneity (Zintzaras and Hadjigeorgiou 2005;Zintzaras and Ioannidis, 2005;Zintzaras, 2007). Random effects modeling assume a genuine diversity in the results of various studies, and it incorporates a between-study variance into the calculations.…”