Journal of Mazandaran University of Medical Sciences
مجله دانشگاه علوم پزشکی مازندران
J Mazandaran Univ Med Sci
Medical Sciences
http://jmums.mazums.ac.ir
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2018
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بررسی پلیمورفیسم ژن های IGSF2 و TNFα و
خطر توسعه مهار کننده در بیماران مبتلا به هموفیلی A
Investigating the IGSF2 and TNFα Genes Polymorphism and the Risk of Inhibitor Development in Patients with Hemophilia A
بیوشیمی
Sports biomechanics
پژوهشي-کامل
Research(Original)
<span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b koodak;">سابقه</span></span></span><span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b koodak;"> و هدف:</span></span></span> <span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">بیماری هموفیلی بیماری وراثتی وابسته به جنس است </span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">که</span></span> <span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">مردها</span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;"> مبتلا و زن</span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;"></span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">ها ناقل آن می</span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;"></span></span><span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">باشند.</span></span> <span style="letter-spacing:-.2pt;"><span style="font-family:b zar;">هموفیلی</span></span> <span dir="LTR"><span style="font-size:10.0pt;">A</span></span> <span style="font-family:b zar;">ناشی از نقص در تولید فاکتور </span><span dir="LTR"><span style="font-size:10.0pt;">VIII</span></span><span style="font-family:b zar;"> می</span><span style="font-family:b zar;"></span> <span style="font-family:b zar;">باشد. در بعضی از بیماران هموفیلی </span><span dir="LTR"><span style="font-size:10.0pt;">A</span></span> <span style="font-family:b zar;">مهارکننده</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">هایی از نوع آنتی</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">بادی</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">های </span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">IgG1</span></span></span> <span style="font-family:b zar;">و </span><span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">IgG4</span></span></span><span style="font-family:b zar;">، بیان می</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">شود که با فاکتور انعقادی مذکور بر همکنش داشته و </span><span style="font-family:b zar;">مانع</span><span style="font-family:b zar;"> از عملکرد آن می</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">شوند. این مطالعه با هدف بررسی ارتباط بین پلیمورفیسم تک نوکلئوتیدی ژن</span><span style="font-family:b zar;"></span><span style="font-family:b zar;">های</span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">IGSF2</span></span></span><span style="color:black;"><span style="font-family:b zar;"> و </span></span><span dir="LTR"><span style="color:black;"><span style="font-size:10.0pt;">TNFα</span></span></span> <span style="color:black;"><span style="font-family:b zar;">با توسعه مهارکننده</span></span><span style="font-family:b zar;"></span><span style="color:black;"><span style="font-family:b zar;">ها در بیماران هموفیلی نوع </span></span><span dir="LTR"><span style="color:black;"><span style="font-size:10.0pt;">A</span></span></span><span style="color:black;"><span style="font-family:b zar;"> انجام پذیرفت.</span></span><br>
<span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b koodak;">مواد و روش</span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;"></span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b koodak;">ها:</span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;"> در این </span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b zar;">مطالعه مورد</span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-size:10.0pt;">-</span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b zar;">شاهدی، 100 <span style="color:black;">فرد دارای هموفیلی نوع </span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-size:10.0pt;">A</span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;"> (55 نفر دارای مهارکننده و 45 نفر بدون مهارکننده) انتخاب شدند و تشخیص مهارکننده، با تست بتسدا انجام شد. از نمونه خون کامل آن</span></span></span><span style="font-family:b zar;"><span style="letter-spacing:-.1pt;"><span style="color:black;">ها، </span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-size:10.0pt;">DNA</span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;"> استخراج گردید و بررسی پلیمورفیسم تک نوکلئوتیدی ژن</span></span></span><span style="font-family:b zar;"><span style="letter-spacing:-.1pt;"><span style="color:black;"> های</span></span></span> <span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">IGSF2</span></span></span><span style="letter-spacing:-.1pt;"><span style="font-family:b zar;"> و </span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">TNFα</span></span></span> <span style="letter-spacing:-.1pt;"><span style="font-family:b zar;">با </span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;">روش </span></span></span><span dir="LTR" style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-size:10.0pt;">Tetra ARMS-PCR</span></span></span><span style="letter-spacing:-.1pt;"><span style="color:black;"><span style="font-family:b zar;"> انجام گرفت.</span></span></span><br>
<span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b koodak;">یافته</span></span></span><span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b zar;"></span></span></span><span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b koodak;">ها:</span></span></span> <span style="color:black;"><span style="font-family:b zar;">دادهها در دو گروه مورد مطالعه از لحاظ تعادل هاردی- واینبرگ بررسی گردید. مقایسه ژنوتیپی ژن</span></span><span style="font-family:b zar;"><span style="color:black;">‏های </span></span><span dir="LTR"><span style="color:black;"><span style="font-size:10.0pt;">IGSF2</span></span></span><span style="color:black;"><span style="font-family:b zar;"> و </span></span><span dir="LTR"><span style="color:black;"><span style="font-size:10.0pt;">TNFα</span></span></span><span style="color:black;"><span style="font-family:b zar;"> نشانگر تفاوت معنی</span></span><span style="font-family:b zar;"><span style="color:black;">دار بین پلیمورفیسم تک نوکلئوتیدی ژن</span></span> <span dir="LTR"><span style="font-family:times new roman,serif;"><span style="font-size:10.0pt;">IGSF2</span></span></span><span style="color:black;"><span style="font-family:b zar;"> و توسعه مهارکننده بوده است </span></span><span style="font-family:b zar;">(</span><span style="font-family:b zar;">018/0 = </span><span dir="LTR"><span style="font-size:10.0pt;">p</span></span><span style="font-family:b zar;">، </span><span dir="LTR"><span style="font-size:10.0pt;">OR</span></span><span style="font-family:b zar;"> برای ژنوتیپهای </span><span dir="LTR"><span style="font-size:10.0pt;">AA</span></span><span style="font-family:b zar;"> و </span><span dir="LTR"><span style="font-size:10.0pt;">AG</span></span><span style="font-family:b zar;">، به ترتیب برابر 39/1 و 37/0). به علاوه، ارتباط معناداری بین دو فاکتور ازدواج فامیلی و عفونت ویروسی با مهارکننده مشاهده شد (05/0 </span><span style="font-family:b zar;"><span style="font-size:10.0pt;">></span></span> <span dir="LTR"><span style="font-size:10.0pt;">p</span></span><span style="font-family:b zar;">). ارتباط بین پاسخ به درمان و آزمون بتسدا نیز تفاوت </span><span style="font-family:b zar;">معنی</span><span style="font-family:b elham;"></span><span style="font-family:b zar;">داری</span><span style="font-family:b zar;"> نشان داده است (002/0 = </span><span dir="LTR"><span style="font-size:10.0pt;">p</span></span><span style="font-family:b zar;">).</span><br>
<span style="letter-spacing:-.2pt;"><span style="color:black;"><span style="font-family:b koodak;">استنتاج:</span></span></span><span style="font-family:b zar;"> با توجه به نتایج به دست آمده می توان گفت که خطر توسعه مهارکنندهها با جهش در ژن </span><span dir="LTR"><span style="font-size:10.0pt;">IGSF2</span></span><span style="font-family:b zar;"> رابطه مستقیمی دارد.</span><br>
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<strong>Background and purpose:</strong> Hemophilia is a hereditary X-linked disorder. Females are carriers and males have the disorder. Hemophilia A is caused by deficiency in the production of factor VIII. In some hemophilia patients, inhibitors including IgG1 and IgG4 antibodies are expressed against this factor. These inhibitors interact with factor VIII and suppress its function. The current study aimed at investigating the relationship between single nucleotide IGSF2 and <a name="_Hlk494131885">TNFα </a>genes polymorphism and development of inhibitors in patients with hemophilia A.<br>
<strong>Materials and methods:</strong> In this case-control study, 100 patients with hemophilia A were selected (55 with inhibitor and 45 without inhibitor). Recognition of inhibitor was performed by Bethesda test. DNA was extracted from whole blood samples. A single-nucleotide polymorphism of IGSF2 and TNFα genes was performed using Tetra ARMS-PCR assay.<br>
<strong>Results:</strong> Hardy-Weinberg equilibrium was investigated in both groups. Comparing the IGSF2 and TNF-α genotypes in these groups indicated a significant correlation between single-nucleotide polymorphism of IGSF2 and development of inhibitors (p<em>=</em> 0.018, odds ratios for AA and AG genotypes were 1.39 and 0.37, respectively). A significant association was seen between incidence of inhibitors and consanguineous marriages and viral infection (p<0.05). Moreover, the association between response to treatment and Bethesda test was significantly different between the two groups (p= 0.002).<br>
<strong>Conclusion:</strong> According to these results, the risk of development of inhibitors has a direct relationship with mutation in IGSF2 gene.<br>
هموفیلی A, مهار کننده, پلیمورفیسم, ژن IGSF2, ژن TNFα
hemophilia A, inhibitor, polymorphism, IGSF2 gene, TNF-α gene
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http://jmums.mazums.ac.ir/browse.php?a_code=A-10-7127-2&slc_lang=fa&sid=1
Afsaneh
Seyed Mikaeili
افسانه
سید میکائیلی