Neda Farajnezhad - Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Pegah Ghandil - Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Maryam Tahmasebi-Birgani - Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz,
Javad Mohammadi-Asl - Noorgene Genetics Laboratory, Ahvaz, Iran.

Background: Cytogenetics and association studies showed that folate gene polymorphisms can increase the risk of chromosomal nondisjunction and aneuploidies. The folate-metabolizing gene polymorphisms in Down syndrome mothers (DSM) have been assessed in a variety of populations. Reduced folate carrier ۱ (RFC۱) and cystathionine beta-synthase (CBS) are key enzymes in folate metabolism. Objective: ۲ common polymorphisms, CBS ۸۴۴ins۶۸ and RFC۱ A۸۰G, were analyzed to determine their probable risk for having Down syndrome (DS) babies in young mothers of Khuzestan province, Iran. Materials and Methods: This study was conducted on ۱۰۰ mothers who had trisomy ۲۱ DS children. ۱۰۰ age- and ethnic-matched mothers with at least ۲ healthy children and no history of abnormal pregnancies were considered as control. The samples were collected from all the mothers from June ۲۰۱۹ to April ۲۰۲۱. Genomic DNA was extracted from peripheral blood. The CBS-۸۴۴ins۶۸ and RFC۱-A۸۰G were genotyped using polymerase chain reaction-electrophoresis and restriction fragment length polymorphism, respectively. Results: The frequency of RFC۱ AG and GG genotypes in DSM was significantly higher than the control mothers (odds ratio [OR] of ۲.۳۸ and ۳.۰۷, respectively). The heterozygote genotype of CBS ۸۴۴ins۶۸ was significantly more prevalent among DSM than the control (OR: ۲.۴۱۹). The OR was significantly increased to ۶.۶۶۷ when the homozygote of both variants was found together. Conclusion: Studying polymorphisms possibly increases the susceptibility of having a DS child. However, ethnicity, nutrition, and epistatic interactions are considerable factors to be evaluated in future studies.

Down syndrome, Folic acid, Polymorphism, CBS, RFC۱., سندروم داون, فولیک اسید, پلی­مورفیسم, CBS, RFC-۱.