Association of glutamate receptor gene polymorphisms with attention-deficit hyperactivity disorder susceptibility: a systematic review and meta-analysis

Abstract

Background: There is a growing body of evidence indicating a possible association between genetic variations and attention-deficit hyperactivity disorder (ADHD), although the results have been inconsistent. The objective of this study was to evaluate the correlation between the GRIN2A, GRIN2B and GRM7 gene polymorphisms and ADHD.Methods: A comprehensive meta-analysis and subgroup evaluation was conducted using a fixed-effects model to analyze the association between ADHD and GRIN2B (rs2284411), GRIN2A (rs2229193), and GRM7 (rs3792452) in six genetic models (dominant, recessive, overdominant, homozygous, heterozygous, and allele models).Results: The meta-analysis comprised 8 studies. The overall analysis showed that the GRIN2B rs2284411 T allele and T carries were significantly associated with a decreased risk of ADHD (dominant model:TT + CT vs. CC: OR = 0.783; 95% CI: 0.627–0.980; p = 0.032, allele model:T vs. C: OR = 0.795; 95% CI: 0.656–0.964; p = 0.019), especially in the Korean subgroup (dominant model:TT + CT vs. CC: OR = 0.640; 95% CI: 0.442–0.928; p = 0.019, overdominant model: CT vs. TT + CC: OR = 0.641; 95% CI: 0.438–0.938; p = 0.022, allele model:T vs. C: OR = 0.712; 95% CI: 0.521–0.974; p = 0.034 and heterozygous model: CT vs. CC: OR = 0.630; 95% CI: 0.429–0.925; p = 0.018). However, no meaningful associations were found for rs2229193 and rs3792452.Conclusion: The results of the meta-analysis provide strong evidence that the rs2284411 T allele is significantly associated with reduced susceptibility to ADHD, particularly in the Korean population.