en ارتباط بین پلی مورفیسم rs8043625 ژن TNP2 و مردان نابارور ایرانی مبتلا به واریکوسل Original Article Original Article <strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">مقدمه: </span></span></strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">مطالعات متعددی ارتباط بین آسیب </span></span><span dir="LTR"><span style="font-size:10.0pt;">DNA</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">اسپرم و واریکوسل را نشان می</span></span><span dir="LTR"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">دهند.</span></span><strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;"></span></span></strong><br> <strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">هدف:</span></span></strong> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">با توجه به نقش حیاتی پروتئین</span></span><span dir="LTR"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">های انتقال هسته</span></span><span dir="LTR"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">ای (</span></span><span dir="LTR"><span style="font-size:10.0pt;">TP</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">) در تراکم و یکپارچگی </span></span><span dir="LTR"><span style="font-size:10.0pt;">DNA</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">اسپرم، این مطالعه مورد-شاهدی برای بررسی تغییرات نوکلئوتید ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">TNP2</span></span></em> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">در بیماران نابارور ایرانی مبتلا به واریکوسل طراحی شد.</span></span><strong><span dir="LTR"><span style="font-size:11.0pt;"></span></span></strong><br> <strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">موارد و روش&shy;ها: </span></span></strong><span dir="LTR"><span style="font-size:10.0pt;">PCR-SSCP</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> و توالی </span></span><span dir="LTR"><span style="font-size:10.0pt;">DNA</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">برای جستجوی جهش در اگزون</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">های 1 و 2 ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">TNP2</span></span></em> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">در 156 بیمار نابارور مبتلا به واریکوسل و 150 مرد بارور بکار برده شد.</span></span><strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;"></span></span></strong><br> <strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">نتایج: </span></span></strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">نتایج توالی یابی سه واریانت در موقعیت</span></span><span dir="LTR"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">های </span></span><span dir="LTR"><span style="font-size:10.0pt;">C.301C> T (p.R101C)</span></span><span style="font-size:10.0pt;">،</span> <span dir="LTR"><span style="font-size:10.0pt;">C.391C> T (p.R131W</span></span><span style="font-size:10.0pt;">) </span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">و </span></span><span dir="LTR"><span style="font-size:10.0pt;">g.IVS1-26G>C (rs8043625</span></span><span style="font-size:10.0pt;">)</span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">در ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">TNP2</span></span></em> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">آشکار کرد. نتایج ما نشان داد که خطر واریکوسل در مردان مبتلا با ژنوتیپ </span></span><span dir="LTR"><span style="font-size:10.0pt;">CC g.IVS1-26G>C</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> بالاتر از کسانی است که این ژنوتیپ&shy;ها را ندارند (بر اساس مدل هم غالبیت، مدل غالبیت، مدل مغلوب و بیش از حد غالب). تجزیه و تحلیل بر اساس هاپلوتایپ نشان داد که هاپلوتایپ&shy;های</span></span><span style="font-size:10.0pt;"> (</span><span dir="LTR"><span style="font-size:10.0pt;">C/C/T</span></span><span style="font-size:10.0pt;">) </span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">و </span></span><span style="font-size:10.0pt;">(</span><span dir="LTR"><span style="font-size:10.0pt;">C/T/T</span></span><span style="font-size:10.0pt;">)</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> عامل خطر در بیماران مبتلا به واریکوسل نسبت به گروه کنترل بود (به ترتیب </span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">278/3 </span></span><span dir="LTR"><span style="font-size:10.0pt;">OR=</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">،</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">000/0 </span></span><span dir="LTR"><span style="font-size:10.0pt;">p=</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> و </span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">304/9 </span></span><span dir="LTR"><span style="font-size:10.0pt;">OR=</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">، </span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">038/0</span></span><span dir="LTR"><span style="font-size:10.0pt;">p=</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">).</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"></span></span><br> <strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">نتیجه &shy;گیری:</span></span></strong> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">با توجه به تفاوت معنی&shy;دار فراوانی ژنوتیپ و آلل </span></span><span dir="LTR"><span style="font-size:10.0pt;">g.IVS1-26G> C</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> در ناحیه اینترونی </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">TNP2</span></span></em> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">در بیماران مبتلا به واریکوسل در مقایسه با گروه کنترل و همچنین با توجه به حفاظت</span></span><span dir="LTR"><span style="font-size:11.0pt;">&shy;</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">شدگی زیاد این موقعیت، این </span></span><span dir="LTR"><span style="font-size:10.0pt;">SNP</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">ممکن است در برخی از فرآیندهای مهم مرتبط با بیان این ژن مانند پیرایش </span></span><span dir="LTR"><span style="font-size:10.0pt;">mRNA</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">دخالت داشته باشد اما مکانیسم دقیق مشخص نیست.</span></span><strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;"></span></span></strong> <strong>Background:</strong> Numerous researches have provided great evidence that revealed the relationship between varicocele and sperm DNA damage.<br> <strong>Objective: </strong>Because of the crucial role of nuclear transition proteins (TPs) in sperm DNA condensation and integrity, this case-control study was designed to study <em>TNP2</em> gene nucleotide variations in Iranian patients with varicocele.<br> <strong>Materials and Methods:</strong> PCR-SSCP and DNA sequencing were used to search for mutations in exons 1 & 2 of the <em>TNP2</em> gene in 156 infertile patients with varicocele and 150 fertile men.<br> <strong>Results:</strong> The results of sequencing showed three variants at positions c.301C>T (p.R101C), c.391C>T (p.R131W), and g.IVS1-26G>C (rs8043625) of <em>TNP2</em> gene. It was found that varicocele risk in men who have the CC genotype of g.IVS1-26G>C SNP is higher than those who don&#39;t have these genotypes (according to Co-dominant model, Dominant model, Recessive model, and Over-dominant model). The haplotype-based analysis showed that (C/C/T) and (C/T/T) haplotypes were a risk factor of in patients with varicocele compared to controls (OR = 3.278, p = 0.000 and OR = 9.304, p = 0.038, respectively).<br> <strong>Conclusion:</strong> Because of the significant difference in the genotype and allele frequencies of g.IVS1-26G>C SNP in the intronic region of <em>TNP2</em> in patients with varicocele compared with controls and also because of the high conservation of this SNP position during evolution, this SNP may be involved in some important processes associated with the expression of this gene like mRNA splicing, but the exact mechanism is not clear. واریکوسل, پلی مورفیسم ژنتیکی, ناباروری, ژن پروتئین انتقال هسته. 557 566 http://ijrm.ir/browse.php?a_code=A-10-1-647&slc_lang=en&sid=1 Mohammad Mehdi Heidari 0000-0002-3328-4746 Yes Department of Biology, Faculty of Science, Yazd University, Yazd, Iran. Amirhossein Danafar 0000-0001-5802-3326 No Department of Biology, Ashkezar Islamic Azad University, Ashkezar, Yazd, Iran Fahime Moezzi 0000-0002-7931-7144 No Department of Biology, Faculty of Science, Yazd University, Yazd, Iran. Mehri Khatami 0000-0002-5840-5399 No Department of Biology, Faculty of Science, Yazd University, Yazd, Iran. Ali Reza Talebi 0000-0003-4883-3020 No Research and Clinical Center for Infertility and Department of Anatomy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.