Choline metabolic pathway gene polymorphisms and risk for Down syndrome: An association study in a population with folate-homocysteine metabolic impairment

• Published in: European journal of clinical nutrition Vol. 71; no. 1; pp. 45 - 50
• Main Authors: Jaiswal, S K, Sukla, K K, Chauhan, A, Lakhotia, A R, Kumar, A, Rai, A K
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.01.2017; Nature Publishing Group
• Subjects: 45; 45/22; 45/29; 45/77; 692/499; Adult; Betaine-Homocysteine S-Methyltransferase - genetics; Case-Control Studies; Child; Choline; Choline - metabolism; Choline Dehydrogenase - genetics; Clinical Nutrition; Dehydrogenase; Down syndrome; Down Syndrome - genetics; Epidemiology; Female; Folic acid; Folic Acid - metabolism; Genes; Genetic aspects; Genetic Association Studies; Genetic polymorphisms; Genotype; Health aspects; Homocysteine; Homocysteine - metabolism; Humans; Internal Medicine; Medicine; Medicine & Public Health; Metabolic Diseases; Metabolic Networks and Pathways - genetics; Metabolism; Mothers; Nutrients; Odds Ratio; original-article; Phosphatidylethanolamine N-Methyltransferase - genetics; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Public Health; Risk Factors; India
• ISSN: 0954-3007; 1476-5640; 1476-5640
• DOI: 10.1038/ejcn.2016.190

Background/objectives: Choline is an essential nutrient involved in one-carbon metabolism, but its role in mechanisms underlying meiotic non-disjunction is poorly known. The relationship between folate-homocysteine metabolic pathway gene polymorphism and Down syndrome (DS) risk has been widely analyzed, but there are limited reports on its correlation with choline metabolism. In the present case–control association study, we investigated the relationship of three single-nucleotide polymorphisms (SNPs) (phosphatidylethanolamine N -methyltransferase ( PEMT) rs12325817, choline dehydrogenase ( CHDH ) rs12676 and homocysteine methyltransferase ( BHMT ) rs3733890) of choline metabolism with risk for DS. Subject/methods: Genotyping of 228 mothers of a down syndrome child (DSM) and 200 control mothers (CMs) for all SNPs was performed by PCR coupled with restriction fragment length polymorphism method. Results: A significantly increased risk for BHMT +742AA genotype with an odds ratio of 4.96 (95% confidence interval (CI): 1.66–14.88, P =0.0036) was observed. For PEMT rs12325817 and CHDH rs12676, no significant difference in allelic and genotypic frequencies was observed. In genotypic combination analysis considering PEMT −744GG/ CHDH +432GG/ BHMT +742GG as the reference combination, PEMT −744GC/ CHDH +432GG/ BHMT +742GG genotypic combination was significantly higher in DSM compared with that in CMs with an odds ratio of 2.061 (95% CI: 1.10–3.86, P =0.0342). We also observed an epistatic interaction between methylenetetrahydrofolate reductase ( MTHFR ) rs1801133 and choline metabolic pathway gene variants. Conclusions: Our findings indicate impaired choline metabolism showing a greater risk for DS, especially in a population associated with homocysteine-folate impairment. Further studies are required to confirm our findings.