en بررسی پلی مورفیسم های CBS 844ins68 و RFC1 A80G و ریسک بروز سندروم داون در مادران جوان ایرانی: یک مطالعه مقطعی Reproductive Genetics Original Article Original Article <div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مطالعات سیتوژنتیک و همراهی نشان داده است که پلی‌مورفیسم‌های ژن&shy;های فولات می‌تواند خطر عدم تفرق صحیح کروموزومی و آنوپلوئیدی را افزایش دهد. پلی‌مورفیسم‌های ژن متابولیسم‌کننده فولات در مادران مبتلا به سندرم داون (</span></span><span dir="LTR" style="font-size:10.0pt">DSM</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) در جمعیت‌های مختلف مورد بررسی قرار گرفته است. حامل فولات کاهش یافته 1 (</span></span><i><span dir="LTR" style="font-size:10.0pt">RFC</span></i><span dir="LTR" style="font-size:10.0pt">-<i>1</i></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) و سیستاتیونین بتا سنتاز (</span></span><i><span dir="LTR" style="font-size:10.0pt">CBS</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) دو آنزیم کلیدی در متابولیسم فولات هستند.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">دو پلی&shy;مورفیسم رایج </span></span><i><span dir="LTR" style="font-size:10.0pt">CBS</span></i><span dir="LTR" style="font-size:10.0pt"> 844ins68</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">RFC-1</span></i><span dir="LTR" style="font-size:10.0pt"> A80G</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> برای تعیین خطر احتمالی آنها در داشتن نوزادان </span></span><span dir="LTR" style="font-size:10.0pt">DS</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مادران جوان استان خوزستان، ایران مورد تجزیه و تحلیل قرار گرفتند.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">مواد و روش &shy;ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">این مطالعه بر روی 100 مادر دارای فرزند سندروم داون تریزومی 21 انجام شد. 100 مادر دارای همخوانی سن و قومیت با حداقل دو فرزند سالم و بدون سابقه بارداری غیرطبیعی به عنوان شاهد در نظر گرفته شدند. همه مادران از استان خوزستان بودند. شرکت</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">کنندگان از ژوئن 2019 تا آوریل 2021 جمع</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">آوری شدند. </span></span><span dir="LTR" style="font-size:10.0pt">DNA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ژنومی از خون محیطی استخراج شد. </span></span><i><span dir="LTR" style="font-size:10.0pt">CBS</span></i><span dir="LTR" style="font-size:10.0pt">-844ins68</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><i><span dir="LTR" style="font-size:10.0pt">RFC-1</span></i><span dir="LTR" style="font-size:10.0pt">-A80G</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> به ترتیب با استفاده از </span></span><span dir="LTR" style="font-size:10.0pt">PCR-electrophoresis</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:10.0pt">RFLP</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ژنوتیپ شدند.</span></span></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">در ارتباط با </span></span><i><span dir="LTR" style="font-size:10.0pt">RFC-1</span></i><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، فراوانی ژنوتیپ</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">های </span></span><span dir="LTR" style="font-size:10.0pt">AG</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و </span></span><span dir="LTR" style="font-size:10.0pt">GG</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در مادران مبتلا به سندرم داون به طور معنی</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">داری بیشتر از مادران شاهد بود (ریسک خطر به ترتیب 38/2 و 07/3). ژنوتیپ هتروزیگوت </span></span><i><span dir="LTR" style="font-size:10.0pt">CBS</span></i><span dir="LTR" style="font-size:10.0pt"> 844ins68</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در بین مادران مبتلا به سندرم داون به طور معنی</span></span><span dir="LTR" style="font-size:11.0pt"><span arial="" style="font-family:">&shy;</span></span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">داری بیشتر از شاهد بود (ریسک خطر 419/2). در نتیجه همزمانی وقوع هموزیگوت هر دو واریانت، ریسک خطر به طور قابل توجهی به 667/6 افزایش یافت.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">نتیجه &shy;گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">پلی&shy;مورفیسم&shy;های مورد مطالعه احتمالاً استعداد داشتن فرزند سندروم داون را افزایش می&shy;دهند. با این حال، قومیت، تغذیه و اپیستازی عوامل قابل توجهی هستند که باید در مطالعات آینده مورد ارزیابی قرار گیرند.</span></span><b><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif""></span></span></b></span></span></span></span></span><br> <br> <span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span new="" roman="" style="font-family:" times=""><b><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">کلمات کلیدی: </span></span></i></b><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">سندروم داون، فولیک اسید، پلی&shy;مورفیسم، </span></span></i><i><span dir="LTR" style="font-size:9.0pt">CBS</span></i><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">، </span></span></i><i><span dir="LTR" style="font-size:9.0pt">RFC-1</span></i><i><span lang="FA" style="font-size:10.0pt"><span b="" mitra="" style="font-family:">.</span></span></i></span></span></span></span></span></div> <p style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="background:white">Background: </span></b>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 1 (<i>RFC1</i>) and cystathionine beta-synthase (<i>CBS</i>) are key enzymes in folate metabolism.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="background:white">Objective: </span></b><span style="background:white">2 common polymorphisms, </span><i>CBS</i> 844ins68 and <i>RFC1</i> A80G, <span style="background:white">were analyzed to determine their probable risk for having </span>Down syndrome <span style="background:white">(DS) babies </span>in young mothers of Khuzestan province, Iran.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="background:white">Materials and Methods:</span> </b>This study was conducted on 100 mothers who had trisomy 21 DS children. 100 age- and ethnic-matched mothers with at least 2 healthy children and no history of abnormal pregnancies were considered as control. The samples were collected from all the mothers from June 2019 to April 2021. Genomic DNA was extracted from peripheral blood. The <i>CBS</i>-844ins68 and <i>RFC1</i>-A80G were genotyped using polymerase chain reaction-electrophoresis and restriction fragment length polymorphism, respectively.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" times=""><b><span style="background:white">Results: </span></b>The frequency of RFC1 AG and GG genotypes in DSM was significantly higher than the control mothers (odds ratio [OR] of 2.38 and 3.07, respectively). The heterozygote genotype of <i>CBS</i> 844ins68 was significantly more prevalent among DSM than the control (OR: 2.419). The OR was significantly increased to 6.667 when the homozygote of both variants was found together.</span></span></span><br> <span style="font-size:12pt"><span style="line-height:normal"><span new="" roman="" times=""><b>Conclusion:</b> 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.</span></span></span><br> &nbsp;</span></p> سندروم داون, فولیک اسید, پلی­مورفیسم, CBS, RFC-1. Down syndrome, Folic acid, Polymorphism, CBS, RFC1. 127 136 http://ijrm.ir/browse.php?a_code=A-10-2457-1&slc_lang=en&sid=1 Neda Farajnezhad farajnezhadn@gmail.com 0000-0001-9202-3944 No Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Pegah Ghandil pghandil@yahoo.com 0000-0001-7828-6465 No Department of Medical Genetics, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. Maryam Tahmasebi-Birgani tahmasebi.birgani62@gmail.com 0000-0002-9624-1903 Yes 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, Iran. Javad Mohammadi-Asl mohammadiasl@gmail.com 0000-0002-1750-0541 No Noorgene Genetics Laboratory, Ahvaz, Iran.