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
1401
7
1
gregorian
2022
10
1
20
10
online
1
fulltext
en
بررسی ارتباط واریانت های rs9340799، rs2234693 در ژن ESR1 و rs243865 در ژن MMP2 در زنان ایرانی مبتلا به کاهش زودرس ذخیره ی تخمدان: یک مطالعه ی مورد-شاهدی
Association Study of ESR1 rs9340799, rs2234693, and MMP2 rs243865 Variants in Iranian Women with Premature Ovarian Insufficiency: A case-control study
Reproductive Genetics
Original Article
Original Article
<div style="text-align: justify;"><span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مقدمه: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">کاهش زودرس ذخیره</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">ی تخمدان (</span></span><span dir="LTR" style="font-size:10.0pt">POI</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">) یک بیماری نادر است که از نظر بالینی با کاهش یا اختلال در عملکرد فولیکول</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">های تخمدان در نظر گرفته می</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">شود و همچنین یائسگی قبل از 40 سالگی به عنوان سن مد نظر برای </span></span><span dir="LTR" style="font-size:10.0pt">POI</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مشخص می</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">شود. این یک بیماری پیچیده است و عوامل متعددی در اتیولوژی آن دخیل هستند. با این حال، عوامل ژنتیکی نقش غالب در استعداد ابتلا به این بیماری دارند.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">هدف: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">هدف این مطالعه بررسی ارتباط ژنتیکی پلی</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مورفیسم</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">های </span></span><span dir="LTR" style="font-size:10.0pt">rs934079</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">ESR1</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و </span></span><span dir="LTR" style="font-size:10.0pt">rs243865</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">MMP2</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> با ریسک ابتلا به بیماری </span></span><span dir="LTR" style="font-size:10.0pt">POI</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در زنان ایرانی می</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">باشد.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مواد و روش ­ها: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">این مطالعه مورد-شاهدی بر روی 150 زن مبتلا به </span></span><span dir="LTR" style="font-size:10.0pt">POI</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و 150 زن سالم (از آبان 1398 تا اردیبهشت 1399) انجام شد. ژنوتایپینگ پلی</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مورفیسم­های ژن </span></span><span dir="LTR" style="font-size:10.0pt">rs934079<i> ESR1</i></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> و در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">MMP2 </span></i><span dir="LTR" style="font-size:10.0pt">rs243865</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> با استفاده از تکنیک </span></span><span dir="LTR" style="font-size:10.0pt">T-ARMS-PCR</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> انجام شد. همچنین آنالیز هاپلوتیپ و عدم تعادل پیوستگی (</span></span><span dir="LTR" style="font-size:10.0pt">LD</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">) توسط نرم افزار آنالیز </span></span><span dir="LTR" style="font-size:10.0pt">SNP</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مورد بررسی قرار گرفت.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">نتایج: </span></span></b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مطالعه ما نشان داد که فراوانی ژنوتیپ</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">های </span></span><span dir="LTR" style="font-size:10.0pt">TT, CC</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> پلی</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مورفیسم </span></span><span dir="LTR" style="font-size:10.0pt">rs243865</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">MMP2</span></i> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و ژنوتیپ</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">های </span></span><span dir="LTR" style="font-size:10.0pt">CC, TT</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در پلی</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مورفیسم </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و ژنوتیپ</span></span><span dir="LTR" style="font-size:11.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">های </span></span><span dir="LTR" style="font-size:10.0pt">GG AA</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در پلی­مورفیسم </span></span><span dir="LTR" style="font-size:10.0pt">rs9340799</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">ESR1</span></i> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در گروه کیس نسبت به گروه کنترل شیوع بیشتری داشتند. علاوه بر این، ژنوتیپهای </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و </span></span><span dir="LTR" style="font-size:10.0pt">rs9340799</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">ESR1</span></i> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">ارتباط معنیداری با ایجاد بیماری در جمعیت ما نشان دادند (05/0 </span></span><span lang="FA" style="font-size:10.0pt">> </span><span dir="LTR" style="font-size:10.0pt">p</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">). در میان چهار هاپلوتیپ برای دو پلی­مورفیسم در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">ESR1</span></i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">، هاپلوتیپ </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693T/rs9340799A</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> با ایجاد خطر برای </span></span><span dir="LTR" style="font-size:10.0pt">POI</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">مرتبط بود.</span></span></span></span></span></span></span><br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">نتیجه ­گیری:</span></span></b> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">پلیمورفیسم </span></span><span dir="LTR" style="font-size:10.0pt">rs2234693</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">و </span></span><span dir="LTR" style="font-size:10.0pt">rs9340799</span><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra""> در ژن </span></span><i><span dir="LTR" style="font-size:10.0pt">ESR1</span></i><i> </i><span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">به شدت با ایجاد بیماری </span></span><span dir="LTR" style="font-size:10.0pt">POI</span> <span lang="FA" style="font-size:11.0pt"><span style="font-family:"B Mitra"">در جمعیت ما مرتبط بود.</span></span></span></span></span></span></span><br>
<br>
<span style="font-size:12pt"><span style="text-justify:inter-ideograph"><span style="direction:rtl"><span style="unicode-bidi:embed"><span style="font-family:"Times New Roman","serif""><b><i><span lang="FA" style="font-size:10.0pt"><span style="font-family:"B Mitra"">کلمات کلیدی:</span></span></i></b><span lang="FA" style="font-size:10.0pt"><span style="font-family:"B Mitra""> <i>ماتریکس متالوپروتئیناز-2، گیرنده استروژن-1، کاهش زودرس ذخیره</i></span></span><i><span dir="LTR" style="font-size:10.0pt"><span style="font-family:"Arial","sans-serif"">­</span></span></i><i><span lang="FA" style="font-size:10.0pt"><span style="font-family:"B Mitra"">ی تخمدان، ناباروری زنان.</span></span></i></span></span></span></span></span></div>
<div style="text-align: justify;"><span style="font-family:Times New Roman;"><span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Background:</span></b><span style="font-size:12.0pt"> Primary ovarian insufficiency (POI) is a rare disease clinically characterized by ovarian follicles depletion or dysfunction and menopause before the age of 40 yr as the cut-off age for POI. It is a complex disease, and its etiology involves several factors. However, genetic factors have a predominant role in the susceptibility to the disease.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Objective:</span></b><span style="font-size:12.0pt"> This study aims to investigate the polymorphisms of </span><span style="font-size:12.0pt">rs243865 in the </span><span style="font-size:12.0pt">matrix metallopeptidase 2 (<i>MMP2</i></span><span style="font-size:12.0pt">) gene and rs2234693 and rs9340799 in the </span><span style="font-size:12.0pt">estrogen receptor 1 </span><i><span style="font-size:12.0pt">(ESR1</span></i><span style="font-size:12.0pt">) gene with susceptibility to POI in Iranian women under 35 yr.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Materials and Methods:</span></b><span style="font-size:12.0pt"> This case-control study was performed on 150 women with POI and 150 healthy women who</span><span style="font-size:12.0pt"> were referred to Yazd Reproductive Sciences Institute, Yazd, Iran between May-October 2020</span><span style="font-size:12.0pt">. The genotyping of <i>ESR1</i> rs9340799, rs2234693, and</span> <i><span style="font-size:12.0pt">MMP2</span></i><span style="font-size:12.0pt"> rs243865 polymorphism was done using tetra-amplification refractory mutation system-polymerase chain reaction. In addition, haplotype analysis and linkage disequilibrium were investigated by SNPanalyzer software.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Results:</span></b><span style="font-size:12.0pt"> Our study revealed the frequency of rs243865 TT, CC genotypes in the <i>MMP2</i> gene and rs2234693 CC, TT; and rs9340799 GG, AA in the <i>ESR1</i> gene were more prevalent in </span><span style="font-size:12.0pt">the case group compared to the control group. In addition, <i>ESR1</i> rs2234693 and rs9340799 genotypes showed significant association with the development of the disease in our population. Among 4 haplotypes for 2 polymorphisms in the <i>ESR1</i> gene, rs2234693T/rs9340799A haplotype was associated with conferring risk to POI.</span></span></span><br>
<span style="font-size:11pt"><span style="line-height:normal"><b><span style="font-size:12.0pt">Conclusion:</span></b> <i><span style="font-size:12.0pt">ESR1</span></i><span style="font-size:12.0pt"> rs2234693 and rs9340799 polymorphism were strongly associated with our population’s POI. </span></span></span></span></div>
ماتریکس متالوپروتئیناز-2, گیرنده استروژن-1, کاهش زودرس ذخیرهی تخمدان, ناباروری زنان.
Matrix metalloproteinase-2, Estrogen receptor alpha, Primary ovarian insufficiency, Female infertility.
841
850
http://ijrm.ir/browse.php?a_code=A-10-2042-1&slc_lang=en&sid=1
Farzaneh
Sadat Eshaghi
Farzaneh.sadat.eshaghi@gmail.com