fa ارتباط پلی‌مورفیسم‌های G1193/C , C2145/T اگزون‌های 8‍‍‍‍ ,12 ژن پراکسیداز تیروییدی و تیتر آنتی‌بادی ضد آن در جمعیت ایرانی ژنتيك Genetic پژوهشی Original <p class="Abstract" dir="rtl" style="MARGIN: 0cm 36pt 0pt 1cm TEXT-INDENT: 3.7pt LINE-HEIGHT: 16pt mso-line-height-rule: exactly"><strong><u><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">مقدمه</span></u><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">: بیماری‌های خود‌ایمنی تیرویید جز بیماری‌های رایج بوده و تعیین وضعیت ژنتیکی آن در سبب‌شناسی بیماری دارای اهمیت است. این پژوهش با هدف بررسی ارتباط دو پلی‌مورفیسم اگزون‌های ‌8 و 12 ژن پراکسیداز تیرویید </span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">(Thyroid Peroxidase)</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span><font face="Lotus"><span style="mso-spacerun: yes"><font size="3">  </font></span>با میزان آنتی‌بادی ضد آن (</font></span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-Thyroid Peroxidase</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>) در جمعیت ایرانی انجام شد. <u>مواد و روش‌ها</u>: از جمعیت مورد بررسی در مطالعه‌ی قند و لیپید تهران، 184 نفر در دو گروه مورد (112 نفر، 100</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO<</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> واحد در لیتر و </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-Tg</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>) و شاهد (72 نفر، 100</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO></span><span dir="rtl"></span><span dir="rtl"></span></font><span style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> <span lang="FA"><font face="Lotus" size="3">واحد در لیتر و </font></span></span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-Tg</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>) انتخاب شدند. سطح سرمی </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> و </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-Tg</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> با روش الیزا</span><span dir="ltr"></span><span dir="ltr"></span><span lang="FA" dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial"> </font></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">اندازه‌گیری گردید. محتوای ‌</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">DNA</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> ژنومی خون محیطی با روش نمک اشباع/ پروتئیناز کا استخراج گردید. اگزون‌های ‌8 و 12 ژن </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> با روش </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">PCR</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> تکثیر شدند و با آنزیم‌های محدودالاثر</span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial"> SacII </font></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">و </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">BsrI</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> انکوبه و پلی‌مورفیسم‌های مورد نظر با روش </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">RFLP</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> بررسی گردیدند. <u>یافته‌ها</u>: فراوانی الل ‌</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">C</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> پلی</span><span dir="ltr" style="FONT-FAMILY: SimSun mso-font-kerning: 16.0pt mso-ascii-font-family: Arial mso-hansi-font-family: Arial">‌</span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">مورفیسم </span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial"><span style="mso-spacerun: yes"> </span>C2145/T</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>(اگزون ‌12) در افراد </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO+ </span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span><font face="Lotus"><span style="mso-spacerun: yes"><font size="3"> </font></span>2/71% و در افراد </font></span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO-</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> 8/28% بود. حضور الل ‌</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">C</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> ارتباط معنی‌داری با افزایش </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> نشان داد: ژنوتیپ ‌</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">CC</span><span dir="rtl"></span><span dir="rtl"></span></font><span style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> <span lang="FA"><font face="Lotus" size="3">100 واحد در لیتر380</font></span></span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">±</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>436 و ژنوتیپ </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">TT</span><span dir="rtl"></span><span dir="rtl"></span></font><span style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> <span lang="FA"><font face="Lotus" size="3">100 واحد در لیتر</font></span></span><span dir="ltr"></span><span dir="ltr"></span><span lang="FA" dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial"> </font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>330</span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">±</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>140 (001/0</span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">(P<</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>. میزان </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> در افراد حامل الل‌</span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">C</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> نسبت به گروه بدون آن نیز افزایش داشت </span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">)</font></span><span dir="rtl"></span><span dir="rtl"></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span>2/9</span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr" style="mso-font-kerning: 16.0pt"><span dir="ltr"></span><span dir="ltr"></span><font face="Arial"> .(OR=</font></span><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt">پلی‌مورفیسم </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">G1193/C</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> (اگزون ‌8) با سطح </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> <span lang="FA"><font face="Lotus" size="3">سرم ارتباط معنی‌داری نداشت. <u>نتیجه‌گیری</u>: بر اساس یافته‌های پژوهش حاضر به‌نظر می‌رسد حضور الل‌</font></span></span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">C</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> پلی‌مورفیسم </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">C2145/T</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> اگزون ‌12 ژن </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> با سطح بالای </span><font face="Arial"><span dir="ltr" style="mso-font-kerning: 16.0pt">Anti-TPO</span><span dir="rtl"></span><span dir="rtl"></span></font><span lang="FA" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt mso-font-kerning: 16.0pt"><span dir="rtl"></span><span dir="rtl"></span> سرم مرتبط بوده و افراد حامل این آلل نسبت به افراد بدون آن 2/9 برابر در معرض کم‌کاری ‌خودایمنی تیرویید قرار دارند. به احتمال زیاد این پلی‌مورفیسم در سبب‌شناسی خودایمنی تیروییدنقش دارد. <p></p></span></strong></p> <p class="Abstract" style="MARGIN: 0cm 1cm 0pt DIRECTION: ltr unicode-bidi: embed TEXT-ALIGN: justify"><font face="Arial"><strong>Abstract</strong></font></p><p class="Abstract" style="MARGIN: 0cm 1cm 0pt DIRECTION: ltr unicode-bidi: embed TEXT-ALIGN: justify"><strong><font face="Arial"><u>Introduction</u>: Autoimmune thyroid diseases (AITD) are common and it is important to identify the genetic determinants. The aim of this study was to assess the relationship between two polymorphisms of Thyroid Peroxidase gene (TPO) and serum level of Anti-TPO titer in an Iranian population. <u>Materials and methods</u>: We selected 184 individuals from <place w:st="on"><city w:st="on">Tehran</city></place> Lipid and Glucose Study, categorized as the Anti-TPO-<span dir="rtl"></span><span dir="rtl"></span></font><span dir="rtl" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt"><span dir="rtl"></span><span dir="rtl"></span> </span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">(n=72) and Anti-TPO+<span dir="rtl"></span><span dir="rtl"></span></font><span dir="rtl" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt"><span dir="rtl"></span><span dir="rtl"></span> </span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr"></span><span dir="ltr"></span><font face="Arial">(n=112) groups. Inclusion criteria for cases was Anti-TPO and Anti-Tg>100U/L with a history of hypothyroidism. Anti-TPO levels in subjects were measured by the ELISA kit. Genomic DNA was extracted using Salting-out/Proteinase K method. Polymorphism detection of Exon 8 and 12 was done using the PCR-RFLP method. The PCR products were incubated with restriction enzymes SacII and BsrI, respectively. <u>Results</u>: The C allele frequency of C2145/T polymorphism Exon 12 (rs732608) was observed in 71.2% of patients and in 28.8% of normal individuals. This allele was significantly associated with increased levels of Anti-TPO [(T 140±330 pmol/L vs. C 436±380 pmol/L P<0.001), (OR: 9.2)]. The G1193/C was not associated with the level of serum Anti-TPO in this study. <u>Conclusion</u>: We demonstrated that the C allele polymorphism in C2145/T exon 12 is associated with high levels of serum Anti-TPO and that carriers of this allele are predisposed to disease 9.2 times more<span style="mso-spacerun: yes">  </span>than those who do not have A allele. <span lang="FA" dir="rtl" style="FONT-SIZE: 11pt FONT-FAMILY: Lotus mso-ansi-font-size: 9.0pt"><p></p></span></font></strong></p><p></p> Anti-TPO ،TPO، پلی‌مورفیسم‌های G1193/C و C2145/T Thyroid peroxidase antibody, Polymorphism, Thyroid Peroxidase gene, Autoimmune hypothyroidism 288 293 http://ijem.sbmu.ac.ir/browse.php?a_code=A-10-287-16&slc_lang=fa&sid=1 Mehdi Hedayati مهدی هدایتی hedayati@endocrine.ac.ir 4000319475328460014701 4000319475328460014701 Yes Obesity Research Center, Researcxh Institute for Endocrine Sciences مرکز تحقیقات پیشگیری و درمان چاقی Marzieh Salehi Jahromi مرضیه صالحی جهرمی 4000319475328460014702 4000319475328460014702 No Obesity Research Center, Researcxh Institute for Endocrine Sciences مرکز تحقیقات پیشگیری و درمان چاقی Laleh Hoghoughi لاله حقوقی راد 4000319475328460014703 4000319475328460014703 No Obesity Research Center, Researcxh Institute for Endocrine Sciences مرکز تحقیقات پیشگیری و درمان چاقی Marjan Zarif yeganeh مرجان ظریف یگانه 4000319475328460014704 4000319475328460014704 No Maryam Daneshpour مریم السادات دانشپور 4000319475328460014705 4000319475328460014705 No Obesity Research Center, Researcxh Institute for Endocrine Sciences مرکز تحقیقات پیشگیری و درمان چاقی Fereidoun Azizi فریدون عزیزی 4000319475328460014706 4000319475328460014706 No Research Instutute for Endocrine Sciences پژوهشکده علوم غدد درون ریز