en تنوع ژنهای کدکننده رسپتورهای هیالورونیک اسید HMMR (rs299295) و STAB2 (rs2271637) با خطر نئوپلاسم پروستات: یک مطالعه موردی-شاهدی و کامپیوتری Reproductive Urology 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:">پروتئین‌های </span></span><span dir="LTR" style="font-size:10.0pt">HMMR</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">STAB2</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> که به عنوان گیرنده&shy;های پروتئین سطح سلولی ماتریکس خارج سلولی (</span></span><span dir="LTR" style="font-size:10.0pt">ECM</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) شناخته می&shy;شوند، به اسید هیالورونیک (</span></span><span dir="LTR" style="font-size:10.0pt">HA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) متصل می&shy;شوند و منجر به عملکردهای مختلف سلولی می&shy;شوند.</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:">این مطالعه با هدف بررسی ارتباط بین واریانت‌های ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">HMMR</span></i><span dir="LTR" style="font-size:10.0pt">-rs299295 (C>T/ A485V)</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">STAB2</span></i><span dir="LTR" style="font-size:10.0pt">-rs2271637 (C>G/ L2401V)</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و خطر ابتلا به نئوپلاسم‌های پروستات در جمعیت مازندران (شمال ایران) انجام شد.</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 به صورت مورد-شاهدی و با رویکرد کامپیوتری انجام شد. ماده </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 598 نمونه خون داخل وریدی شامل 250 نئوپلاسم از هیپرپلازی خوش&shy;خیم پروستات (</span></span><span dir="LTR" style="font-size:10.0pt">BPH</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">) و 250 نئوپلاسم بدخیم پروستات (سرطان پروستات) به عنوان بیمار (مورد) و 98 مرد سالم به عنوان کنترل استخراج شد. ژنوتیپ&shy;های </span></span><i><span dir="LTR" style="font-size:10.0pt">HMMR</span></i><span dir="LTR" style="font-size:10.0pt">-rs299295</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">STAB2</span></i><span dir="LTR" style="font-size:10.0pt">-rs2271637</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با استفاده از روش </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:"> مشخص شدند. تجزیه و تحلیل بیوانفورماتیک با استفاده از ابزارهای برخط رایگان </span></span><span dir="LTR" style="font-size:10.0pt">PolyPhen-2</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">، </span></span><span dir="LTR" style="font-size:10.0pt">GOR IV</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">GeneMANIA</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> انجام شد.</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:">این مطالعه نشان داد که آلل </span></span><span dir="LTR" style="font-size:10.0pt">T</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> جهش&shy;یافته در </span></span><i><span dir="LTR" style="font-size:10.0pt">HMMR</span></i><span dir="LTR" style="font-size:10.0pt">-rs299295</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و آلل </span></span><span dir="LTR" style="font-size:10.0pt">G</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در </span></span><i><span dir="LTR" style="font-size:10.0pt">STAB2</span></i><span dir="LTR" style="font-size:10.0pt">-rs2271637</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> با افزایش خطر نئوپلاسم پروستات، از جمله </span></span><span dir="LTR" style="font-size:10.0pt">BPH</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> و سرطان پروستات مرتبط هستند (با 001/0 </span></span><span lang="FA" style="font-size:10.0pt">> </span><span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">). تجزیه و تحلیل بیوانفورماتیک، تغییرات ساختاری و آسیب احتمالی از این واریانت‌های جهش&shy;یافته را نشان داد. واریانت </span></span><i><span dir="LTR" style="font-size:10.0pt">HMMR</span></i><span dir="LTR" style="font-size:10.0pt">-A485V</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ممکن است برهمکنش با </span></span><span dir="LTR" style="font-size:10.0pt">FAM83D</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را مختل کند و واریانت </span></span><i><span dir="LTR" style="font-size:10.0pt">STAB2</span></i><span dir="LTR" style="font-size:10.0pt">-L2401V</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> می&shy;تواند دامین هفتم از </span></span><span dir="LTR" style="font-size:10.0pt">FAS1</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> را مختل کند که در مجموع ممکن است بر تعامل فیزیکی پروتئین، به ویژه با </span></span><span dir="LTR" style="font-size:10.0pt">MAPK1</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> تأثیر بگذارند.</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:">نتیجه&shy; گیری: </span></span></b><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:">آلل&shy;های جهش&shy;یافته </span></span><span dir="LTR" style="font-size:10.0pt">T</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در </span></span><i><span dir="LTR" style="font-size:10.0pt">HMMR</span></i><span dir="LTR" style="font-size:10.0pt">-rs299295</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">G</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> در </span></span><i><span dir="LTR" style="font-size:10.0pt">STAB2</span></i><span dir="LTR" style="font-size:10.0pt">-rs2271637</span><span lang="FA" style="font-size:11.0pt"><span b="" mitra="" style="font-family:"> ممکن است ساختارهای پروتئینی را مختل کنند و احتمالاً به پیشرفت نئوپلاسم پروستات کمک کنند.</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></div> <div style="text-align: justify;"><span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Background:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> Hyaluronan-mediated motility receptor (HMMR) and Stabilin-2 (STAB2), known as extracellular matrix cell surface protein&rsquo;s receptors, bind to hyaluronic acid and lead to various cell functions.</span></span><span dir="RTL" lang="FA" style="font-size:12.0pt"><span style="font-family:"Times New Roman","serif""></span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Objective:</span></span></b> <span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">The study aims to investigate the relationship between the <i>HMMR</i>-rs299295 (C>T/ A485V) and <i>STAB2</i>-rs2271637 (C>G/ L2401V) gene variants and the risk of prostate neoplasms in the Mazandaran population, North of Iran.</span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Materials and Methods:</span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times=""> This study was conducted based on a case-control and <i>in silico</i> approach. Genomic DNA was extracted from 598 intravenous blood samples, collected from 250 benign prostatic hyperplasia (case group I) and 250 malignant prostate (case group II) neoplasms as cases, and 98 healthy men as control. The <i>HMMR</i>-rs299295 and <i>STAB2</i>-rs2271637 genotypes were identified using the polymerase chain reaction-restriction fragment length polymorphism method. Bioinformatics analyses were conducted using PolyPhen-2, GOR IV, and GeneMANIA free web tools. </span></span></span></span></span></span><br> <span style="font-size:11pt"><span style="line-height:normal"><span style="text-autospace:none"><span calibri="" style="font-family:"><b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">Results: </span></span></b><span style="font-size:12.0pt"><span new="" roman="" style="font-family:" times="">The study found that the mutant T allele in <i>HMMR</i>-rs299295 and the G allele in <i>STAB2</i>-rs2271637 are associated with an increased risk of prostate neoplasm, including benign prostatic hyperplasia and prostate cancer (p < 0.001). Bioinformatic analyses revealed structural changes and potential damage from these variants. The <i>HMMR</i>-A485V variant might impair interaction with family with sequence similarity 83 member D, and the <i>STAB2</i>-L2401V variant could disrupt domain 7 of FAS1, together they may affect the protein&#39;s physical interactions, especially with mitogen-activated protein kinase 1.</span></span></span></span></span></span><br> <b><span style="font-size:12.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">Conclusion:</span></span></span></b> <span style="font-size:12.0pt"><span style="line-height:107%"><span new="" roman="" style="font-family:" times="">The mutant alleles of T in <i>HMMR</i>-rs299295 and the G in <i>STAB2</i>-rs2271637 may disrupt protein structures and probably contribute to prostate neoplasm progression.</span></span></span></div> FAM83D, Fasciclin-like, HMMR, MAPK1, نئوپلاسم پروستات, STAB2. FAM83D, Fasciclin-like, HMMR, MAPK1, Prostate neoplasm, STAB2. 251 264 http://ijrm.ir/browse.php?a_code=A-10-2866-1&slc_lang=en&sid=1 Hayder Abdulhadi Saleh Albdairi ramahi.h.82@gmail.com 0009-0007-6008-337X No Department of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, Iran. Abasalt Hosseinzadeh Colagar acolagar@yahoo.com 0000-0001-6536-8250 Yes Department of Molecular and Cell Biology, Faculty of Basic Science, University of Mazandaran, Babolsar, Iran.