Journal of Advanced Biomedical Sciences
مجله علوم زیست پزشکی پیشرفته
J Adv Biomed Sci.
Medical Sciences
http://jabs.fums.ac.ir
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بررسی ارتباط چندشکلی تک نوکلئوتیدی rs17859812 پروموتر ژن MUC5AC با خطر ابتلا به سرطان معده
Investigating the Association between rs17859812 Polymorphism in MUC5AC Gene Promoter and Risk of Gastric Cancer
ژنتيك پزشكي
Medical Genetics
پژوهشي
Research
<p dir="RTL" style="margin-right: -1.1pt;"><strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">زمینه و هدف:</span></span></span></strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> ژن</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;"> MU5AC </span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">با کد کردن یکی از موسین</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">های اصلی ترکیب موکوس مخاط معده، نقش مهمی در حفظ مخاط معده در برابر فاکتورهای آسیب</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">زا دارد و بیان آن در سرطان معده کاهش می</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">یابد. با توجه به تأثیر چندشکلی</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">های ناحیه پروموتری در بیان ژن</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">ها، در این مطالعه ارتباط چندشکلی تک نوکلئوتیدی ناحیه پروموتری ژن</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;"> MU5AC </span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">با خطر ابتلا به سرطان معده</span></span></span> <span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">بررسی میشود.</span></span></span><br>
<strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">مواد و روشها:</span></span></span></strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> در این مطالعه مورد- شاهدی، ابتدا قسمتی از ناحیه پروموتر ژن </span></span></span><em><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">MUC5AC</span></span></span></span></em><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> با تکنیک </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">PCR</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> در 50 فرد تکثیرشده و پس از توالی</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">یابی، چند</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">شکلی تک نوکلئوتیدی </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">rs17859812</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> انتخاب شد و بقیه افراد با تکنیک </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">PCR-RFLP</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> تعیین ژنوتیپ شدند. درنهایت، نتایج با آزمونهای آماری رگرسیون لجستیک و کای 2 </span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">آنالیز شد.</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;"></span></span></span></span><br>
<strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">نتایج:</span></span></span></strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> پس از توالی</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">یابی و </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">PCR-RFLP</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> مشخص شد که آلل </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">C</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> در ناحیه -221 پروموتر خطر ابتلا به سرطان معده را افزایش می</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">دهد (008/0</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">P=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 18/09-5/3</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">CI=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 66/1</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">OR=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">) و ژنوتیپ </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">CC</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> با خطر ابتلا به سرطان معده ارتباط دارد (001/0</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">P<</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 38/09-10/2</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">CI=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 66/4</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">OR=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">). همچنین ژنوتیپ </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">CC + CT</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> خطر ابتلا به سرطان معده را افزایش می</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">­</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">دهد (007/0</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">P=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 45/1-7/3</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">CI=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">، 08/2</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">OR=</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">).</span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"></span></span></span><br>
<strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">نتیجهگیری:</span></span></span></strong><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> نتایج این مطالعه نشان داد که آلل </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">C</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> در چندشکلی </span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">rs17859812</span></span></span></span><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> ژن </span></span></span><em><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">MUC5AC</span></span></span></span></em><span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;"> با خطر ابتلا به سرطان معده ارتباط دارد. ازآنجاییکه این چندشکلی در مجاورت جایگاه اتصالی گیرنده گلوکوکورتیکوئید است، احتمالاً از این طریق بر بیان ژن </span></span></span><em><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;">MUC5AC</span></span></span></span></em> <span style="color:black;"><span style="font-family:b nazanin;"><span style="font-size:10.0pt;">و در استعداد افراد به سرطان معده تأثیر دارد.</span></span></span><span dir="LTR"><span style="color:black;"><span style="font-family:times new roman,serif;"><span style="font-size:8.0pt;"></span></span></span></span></p>
<p style="margin-left: -1.1pt;"><strong>Background & Objective:</strong> MU5AC gene plays a key role in the maintenance of gastric mucosa against harmful factors in the stomach through encoding a main mucin of mucus lining gastric mucosa and its expression is reduced in the gastric cancer. In this study, due to the effect of genetic polymorphisms in the promoter region on the gene expression, the association between single nucleotide polymorphism of MU5AC gene promoter and the risk of gastric cancer was assessed.<br>
<strong>Materials & Methods:</strong> in this case-control study, a fragment of MUC5AC gene promoter was amplified by PCR technique in 50 individuals and rs17859812 single nucleotide polymorphism was selected by sequencing, and other subjects were genotyped using PCR-RFLP method. Finally, logistic regression and chi-square tests were used for data analysis.<br>
<strong>Results:</strong> Following sequencing and PCR-RFLP, the findings showed that allele C in the -221 of the promoter increased the risk of gastric cancer (OR= 1.66, CI= 3.09-5<span dir="RTL">.</span>18, p = 0.008) and CC genotype increased the risk of gastric cancer (OR= 4.66, CI= 2.09-10.38, p< 0.001). Also, CC + CT genotypes increased the risk of gastric cancer (OR=2.08, CI= 3.1-7.45 p= 0.007).<br>
<strong>Conclusion:</strong> The results of this study showed that allele C in the rs17859812 polymorphism of the MUC5AC gene is associated with the risk of gastric cancer. As this polymorphism is located in the vicinity of the glucocorticoid receptor binding site, it may affect the MUC5AC gene expression and may result in gastric cancer susceptibility.<span dir="RTL"></span><br>
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ژن MUC5AC, مخاط معده, سرطان معده, چندشکلی تک نوکلئوتیدی, rs17859812
MUC5AC Gene, Gastric Mucosa, Gastric Cancer, Single Nucleotide Polymorphism, rs17859812
530
537
http://jabs.fums.ac.ir/browse.php?a_code=A-10-748-2&slc_lang=fa&sid=1
Mehdi
Moghanibashi
مهدی
مغنی باشی
mehdimoghani@yahoo.com
4432338997
100319475328460017781
Yes
Department of Genetics, School of Medicine, Kazerun Branch, Islamic Azad University, Kazerun, Shiraz, Iran
گروه ژنتیک، دانشکده پزشکی، واحد کازرون، دانشگاه آزاد اسلامی، ایران