Генетика человека и эмбриология

The Association between the MTR Gene A2576G Polymorphism and Alzheimer?s Disease: a Meta Analysis Study

Abstract

Yun Wang, Shunliang Xu and Jianzhong Bi

Background: Alzheimer’s disease (AD) individuals are characterized with high homocysteine (HCY) and low folate blood levels. Polymorphisms of genes encoding critical enzymes in folate metabolism have been associated with hyperhomocysteinemia and AD risk. An adenine to guanine transition at position 2756 (rs185087) of the methionine synthase (MS or MTR) gene causes hyperhomocysteinemia. However, the association between MTR A2756G polymorphism and AD remains controversial. We performed a Meta analysis pooling data from all relevant studies including cases and controls to reexamine the association between the MTR gene A2576G polymorphism and AD. Methods: We applied random-effects or fixed-effects model according to the degree of heterogeneity to combine odds ratio (OR) and 95% coincidence intervals (95% CI). And we used the Quanto 1.2.4 software to calculate genetic power. Egger’s test was carried out to evaluate the potential publication bias. Results and discussion: Eight case-control studies enrolling 2,880 cases and 2,807 controls were included in this meta analysis. The overall ORs with 95% CIs showed no statistical association between the MTR gene A2756G polymorphism and the risk of AD in the allele contrast, the recessive model or dominant model for allele A (randomeffects pooled OR 1.09, 95% CI 0.92-1.30; random-effects pooled OR 1.11, 95% CI 0.91-1.35; fixed-effects pooled OR 1.13, 95% CI 0.83-1.54, respectively). The genetic power was 11.6% in the recessive model and 43.7% in the dominant model. No association between MTR A2756G polymorphism and AD was observed, but the conclusion based on relatively small numbers of participants. Large heterogeneity was detected among combined populations in the contrast of AA vs. AG+GG (p = 0.019, I2 = 56.3%) and A vs. G (p = 0.016, I2 = 57.5%). One study was considered as the main cause of heterogeneity in both contrasts. The heterogeneity doesn’t reduce in the subgroup analyses stratified by racial descents. It can be presumed that the heterogeneity mainly results from the diagnosis of AD and genotyping methods. No publication bias was observed. Conclusions: In conclusion, the present Meta analysis suggests that MTR A2756G polymorphism is not a genetic determinant of AD. But small sample size may be one reason and it could not be ruled out that a true association exists.