International Journal of Reproductive BioMedicine
International Journal of Reproductive BioMedicine
IJRM
Medical Sciences
http://ijrm.ir
1
admin
2476-4108
2476-3772
10.29252/ijrm
en
jalali
1398
4
1
gregorian
2019
7
1
17
7
online
1
fulltext
en
بررسی ارتباط واریانت Q472H در ژن KDR با از دست رفتن مکرر بارداری در جنوب ایران: یک مطالعه مورد شاهدی
The association of Q472H variant in the KDR gene with recurrent pregnancy loss in Southern Iran: A case-control study
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;">سقط مکرر خود</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">به</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">خودی</span></span><span dir="LTR"><span style="font-size:11.0pt;"> (</span></span><span dir="LTR"><span style="font-size:10.0pt;">RSA</span></span><span dir="LTR"><span style="font-size:11.0pt;">) </span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">یک مشکل باروری است که اغلب برای بیماران و متخصصان ناشناخته و غیر</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">قابل تشخیص باقی می</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">ماند. علل احتمالی سقط مکرر خود</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">به</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">خودی ممکن است عوامل ژنتیکی و یا غیر</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">ژنتیکی باشد</span></span><span dir="LTR"><span style="font-size:11.0pt;">.</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> کیفیت گردش خون جفتی برای لانه</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">گزینی و تکوین جنین در طول دوران بارداری از اهمیت کلیدی برخوردار است. گزارش شده گیرنده تیروزین کینازی (</span></span><span dir="LTR"><span style="font-size:10.0pt;">KDR</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">) که (</span></span><span dir="LTR"><span style="font-size:10.0pt;">VEGFR-2</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">) نیز نامیده می</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">شود، با </span></span><span dir="LTR"><span style="font-size:10.0pt;">RSA</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">به دلیل تأثیرات رگ</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">زایی در جفت از طریق مسیر </span></span><span dir="LTR"><span style="font-size:10.0pt;">VEGF-KDR</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> در ارتباط است.</span></span><span dir="LTR"><span style="font-size:11.0pt;"></span></span><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;">در این مطالعه، ارتباط واریانت </span></span><span dir="LTR"><span style="font-size:10.0pt;">Q472H</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> در اگزون 11،</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">ژن کد</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">کننده "گیرنده فاکتور رشد آندوتلیال عروقی" </span></span><span dir="LTR"><span style="font-size:10.0pt;">KDR</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">با سقط</span></span><span dir="LTR"><span style="font-size:11.0pt;">­</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">های مکرر در منطقه جنوب ایران مورد بررسی قرار گرفته است.</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 روش­ها: </span></span></strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;">در این مطالعه مورد-شاهدی 50 نمونه از بافت جنین سقط شده از مادرانی که حداقل دو بار سقط متوالی را تجربه کرده باشند به عنوان گروه مورد و خون بند ناف از 50 نوزاد تازه متولد شده که ماداران آن</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">ها حداقل یک نوزاد ترم زایمان داشتند به عنوان گروه شاهد مورد بررسی قرار گرفت.</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;"> تعیین ژنوتیپ با استفاده از تکنیک </span></span><span dir="LTR"><span style="font-size:10.0pt;">Real-Time PCR</span></span> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">و آنالیز منحنی ذوب با تفکیک بالا (</span></span><span dir="LTR"><span style="font-size:10.0pt;">HRM</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">) انجام گردید.</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;">با در نظر گرفتن ژنوتیپ </span></span> <span dir="LTR"><span style="font-size:10.0pt;">AA</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">به عنوان مرجع، مشخص شد که آلل (</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">029/0</span></span><span dir="LTR"><span style="font-size:10.0pt;">p</span></span><span dir="LTR"><span style="font-size:10.0pt;">=</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;">468/5-095/1 </span></span><span dir="LTR"><span style="font-size:10.0pt;">CI=</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> 95% ،</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">447/2</span></span> <span dir="LTR"><span style="font-size:11.0pt;">(</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;">و همچنین ژنوتیپ هتروزیگوت (</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">016/0</span></span><span dir="LTR"><span style="font-size:10.0pt;">p</span></span><span dir="LTR"><span style="font-size:11.0pt;">=</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;">673/6-210/1 </span></span><span dir="LTR"><span style="font-size:10.0pt;">CI=</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> 95% ،</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">824/2</span></span> <span dir="LTR"><span style="font-size:11.0pt;">(</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;">ارتباط معنی داری با افزایش خطر سقط نشان می</span></span><span style="font-size:11.0pt;">­</span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">دهند.</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 گیری:</span></span></strong> <span style="font-family:b mitra;"><span style="font-size:11.0pt;">ارتباط مستقیمی بین پلی­مورفیسم (</span></span><span dir="LTR"><span style="font-size:10.0pt;">Q472H</span></span><span style="font-family:b mitra;"><span style="font-size:11.0pt;">) ژن </span></span><em><span dir="LTR"><span style="font-size:10.0pt;">KDR</span></span></em><span style="font-family:b mitra;"><span style="font-size:11.0pt;"> با سقط مکرر خود­به­خودی در جنوب ایران مشاهده شد.</span></span><strong><span style="font-family:b mitra;"><span style="font-size:11.0pt;"></span></span></strong><br>
<strong>Background:</strong> Recurrent spontaneous abortion (RSA) often remains unclear and can be burden for the patient and time consuming for clinician. RSA may initiates from a genetic or non-genetic factors. It is well known that the quality of placental circulation is critical for implantation and embryo development. Because of angiogenic effects of VEGF–KDR pathway on placenta, the genes involved in this pathway (the KDR or VEGFR genes) are thought to be linked with RSA.<br>
<strong>Objective:</strong> The aim of this study was to investigate the relationship between Gln472His (A/T) polymorphism of the KDR gene with RSAs in southern Iran.<br>
<strong>Materials and Methods:</strong> In this case-control study, 50 aborted embryonic tissue obtained from fetuses and 50 umbilical cord blood of newborn babies were studied.<br>
Fetal sample from mothers with history of at least two consecutive miscarriages and controls from mothers who had at least one full-term infants born were taken. Genomic DNA was extracted by using PureLink genomic DNA kit (Life Technologies, CA). The Rotor-Gene Q real-Time PCR machine and High-resolution melting curve analysis (HRM) technique were used for genotyping.<br>
<strong>Results:</strong> Based on the AA genotype as reference, it is shown that the T allele (OR =2.447, 95% CI = 1.095–5.468, p = 0.029) as well as AT heterozygote genotype was significantly associated with an increased risk of miscarriage (OR = 2.824, 95% CI = 1.210-6.673, p = 0.016).<br>
<strong>Conclusion:</strong> A positive correlation between Q472H polymorphism of the KDR gene and RSA may be the cause in southern Iran.
سقط, VGEFR 2, پلی مورفیسم.
Abortion, VEGFR 2, Polymorphism
473
480
http://ijrm.ir/browse.php?a_code=A-10-1-637&slc_lang=en&sid=1
Leila
Keshavarz