A Pilot Study on the Contribution of Folate Gene Variants in the Cognitive Function of ADHD Probands
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Genetic abnormalities in components important for the folate cycle confer risk for various disorders since adequate folate turnover is necessary for normal methylation, gene expression and chromosome structure. However, the system has rarely been studied in children diagnosed with attention deficit hyperactivity disorder (ADHD). We hypothesized that ADHD related cognitive deficit could be attributed to abnormalities in the folate cycle and explored functional single nucleotide polymorphisms in methylenetetrahydrofolate dehydrogenase (rs2236225), reduced folate carrier (rs1051266), and methylenetetrahydrofolate reductase (rs1801131 and rs1801133) in families with ADHD probands (N = 185) and ethnically matched controls (N = 216) recruited following the DSM-IV. After obtaining informed written consent for participation, peripheral blood was collected for genomic DNA isolation and PCR-based analysis of target sites. Data obtained was analyzed by UNPHASED. Interaction between sites was analyzed by the multi dimensionality reduction (MDR) program. Genotypic frequencies of the Indian population were strikingly different from other ethnic groups. rs1801133 “T” allele showed biased transmission in female probands (p < 0.05). Significant difference in genotypic frequencies for female probands was also noticed. rs1801131 and rs1801133 showed an association with low intelligence quotient (IQ). MDR analysis exhibited independent effects and contribution of these sites to IQ, thus indicating a role of these genes in ADHD related cognitive deficit.
KeywordsADHD Folate genes MTHFR IQ
Active participation of the volunteers for the study is gratefully acknowledged. Part of this work was presented at the 4th World ADHD Congress held in Milan, Italy during 6th–9th June, 2013, PP# 15-5.
Conflict of interests
The authors declare that there is no conflict of interests regarding the research, authorship and publication of this article.
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