en هایپومتیلاسیون DNA در پروموتر ژن (NR5A1) nuclear receptor subfamily 5 group A member1 مرتبط با اندومتریوز زنان در شمال غرب ایران علوم مولکولی Molecular Sciences تحقیقی Original article <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">زمینه</span></span></strong> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و</span></span></strong> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">هدف: </span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">رشد</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بافت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آندومتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">فعالیت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آن در خارج</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">از</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">رحم</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">باعث ایجاد اندومتریوز می شود</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">. </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شواهد</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نشان می</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">دهد</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">که</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">انحرافات</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مختلف</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اپی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژنتیکی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نقش</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اساسی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پاتوژنز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بازی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">می</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">کند.</span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1</span></span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">یک</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">عامل</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">رونویسی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ضروری،</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">برای</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بیوسنتز استروژن</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">سلول های</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوتیک</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">است.</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بیان</span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و عدم بیان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آن</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آندومتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">درجه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اول</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">توسط</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">متیلاسیون</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پروموتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آن</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">تعیین</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">می</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شود. مطالعه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">حاضر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">با</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">هدف</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مقایسه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">وضعیت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">متیلاسیون</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ناحیه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پروموتری</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژن</span></span> <em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">زنان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مبتلا</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">به</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز و سالم</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">انجام</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">گرفت</span></span><span dir="LTR"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">.</span></span></span><strong><span dir="LTR"><span style="font-family:b zar,bold;"><span style="font-size:12.0pt;"></span></span></span></strong><br> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">روش بررسی: </span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مطالعه</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> موردی </span></span><span style="font-family:sakkal majalla;"><span style="font-size:12.0pt;">&ndash;</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> شاهدی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">حاضر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">از</span></span><span dir="LTR"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> 25 </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نمونه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بافت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوتیک</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">از</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">زنان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مبتلا</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">به</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و</span></span><span dir="LTR"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> 5 </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نمونه</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بافت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آندومتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">طبیعی از افراد تحت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">عمل</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">هیسترکتومی</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> که از بیمارستان‌های ولیعصر، طالقانی، 29 بهمن و شمس شهر تبریز در سال‌ 1395 جمع‌آوری گردید</span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">،</span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">DNA </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">استخراج</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شد.</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نمونه های</span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">DNA </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">حاصل</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بی سولفیته</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شدند</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نهایت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">وضعیت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">متیلاسیون</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پروموتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژن </span></span>&nbsp;<em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">&nbsp;توسط </span></span>&nbsp;<span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">methylation specific</span></span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">PCR</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">مورد</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ارزیابی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">قرار</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">گرفت</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;"> .</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">آنالیز آماری </span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شامل دو قسمت آمار توصیفی و آمار استنباطی</span></span> <span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">با استفاده از </span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نرم افزار آماری </span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">spss</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> نسخه 20 <span style="color:black;">و آزمون استقلال </span>انجام شد.</span></span><strong><span dir="LTR"><span style="font-family:b zar,bold;"><span style="font-size:12.0pt;"></span></span></span></strong><br> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">یافته</span></span></strong> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ها: </span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">میزان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">متیلاسیون</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پروموتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژن</span></span> <em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نمونه های</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوتیک</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">سطح کاهش</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">یافته</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">و با</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ارتباط</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">معنی داری</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">دارد</span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"> (</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">05/0</span></span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">P<</span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">)</span></span></span><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">.</span></span><br> <strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بحث و نتیجه گیری: </span></span></strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">هیپو</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">متیلاسیون</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پروموتر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژن</span></span> <em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">می تواند</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">باعث</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">افزایش</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نسبی</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بیان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ژن</span></span> <em><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:12.0pt;">SF-1 </span></span></span></em><span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بافت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">اندومتریوز</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شود</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">که این</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">افزایش</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بیان</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">در</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">نهایت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ممکن</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">است</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">منجر</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">به</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">ایجاد</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">یا</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">پیشرفت</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">بیماری</span></span> <span style="font-family:b nazanin;"><span style="font-size:12.0pt;">شود.</span></span><strong><span style="font-family:b nazanin;"><span style="font-size:12.0pt;"></span></span></strong> <strong>Background and objectives:</strong> Endometrial tissue growth and its activity outside the uterus cause endometriosis. It has been suggested that various epigenetic deviations play a major role in the pathogenesis of endometriosis. Steroidogenic factor 1 (SF-1; NR5A1) is an essential transcription factor for estrogen biosynthesis in endometrial cells. The expression of SF-1 in endometriosis and lack of expression in normal endometrium is primarily determined by its promoter methylation. Here, we aimed to compare the methylation status of the SF-1 gene promoter region in women with endometriosis in comparison to healthy subjects.<br> <strong>Methods:</strong> In the present case&ndash;control study, DNA was extracted from 25 endometrial tissue samples from women with endometriosis and 5 normal post-hysterectomy endometrium tissues which were collected from Tabriz hospitals including Vali-e-Asr, Taleghani, 29 Bahman and Shams in 2016. The obtained DNA samples were subjected to Bisulfite-treatment. Finally, the status of SF-1gene promoter methylation was evaluated by methylation specific PCR method. Statistical analyses including descriptive and inferential statistics were conducted using tables, bar charts by statistical software SPSS version 20 and independence test.<br> <strong>Results:</strong> The methylation status of SF-1 gene promoter was decreased significantly in endometriosis samples (P<0.05).&nbsp;&nbsp;<br> <strong>Conclusion:</strong> SF-1 gene promoter hypomethylation could increase the relative expression of SF-1 gene in endometriosis which may lead to the development or progression of the disease. اندومتریوز, متیلاسیون پروموتر, ژن Steroidogenic factor 1,NR5A1 Endometriosis, Promoter Methylation, Steroidogenic Factor 1 Gene, NR5A1 1 11 http://goums.ac.ir/jorjanijournal/browse.php?a_code=A-10-24-113&slc_lang=en&sid=1 Soraya Larki ثریا لرکی 10031947532846003642 10031947532846003642 No MSc of Genetic, Department of Biology, Islamic Azad University, Tabriz Branch, Tabriz, Iran کارشناسی ارشد ژنتیک، گروه زیست شناسی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران Masoud Maleki مسعود ملکی maleki.masuod@gmail.com 10031947532846003643 10031947532846003643 Yes Assistant Professor, Department of Biology, Islamic Azad University, Tabriz Branch, Tabriz, Iran استادیار، گروه زیست شناسی، واحد تبریز، دانشگاه آزاد اسلامی، تبریز، ایران