S K Jaiswal1, K K Sukla2, A Chauhan3, A R Lakhotia4, A Kumar5, A K Rai1. 1. Centre for Genetic Disorders, Banaras Hindu University, Varanasi, Uttar Pradesh, India. 2. Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, Uttar Pradesh, India. 3. Applied Microbiology, Department of Botany, Banaras Hindu University, Varanasi, Uttar Pradesh, India. 4. Department of Gynecology, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India. 5. Department of Pediatrics, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Abstract
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.
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 PEMTrs12325817 and CHDHrs12676, 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.
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