بررسی ارتباط پلی‌مورفیسم‌های عوامل انعقادی در زنان مبتلا به میوم رحمی

عرب‌نژاد, محدثه; ابراهیمی, احمد; نصیری, محبوبه; کریمی, مهران

بررسی ارتباط پلی‌مورفیسم‌های عوامل انعقادی در زنان مبتلا به میوم رحمی

نوع مقاله : مقاله های پژوهشی

نویسندگان

¹ کارشناس ارشد، گروه زیست شناسی، دانشگاه آزاد اسلامی، واحد ارسنجان، ارسنجان، ایران

² استادیار، مرکز تحقیقات سلولی مولکولی، پژوهشکده‌ی علوم غدد درون‌‌ریز و متابولیسم، دانشگاه علوم پزشکی شهید بهشتی، تهران، ایران

³ استادیار، گروه زیست شناسی، دانشگاه آزاد اسلامی، واحد ارسنجان، ارسنجان، ایران

⁴ دانشیار، مرکز تحقیقات هماتولوژی، دانشگاه علوم پزشکی شیراز، شیراز، ایران

چکیده

مقدمه: میوم‌ها (لیومیوم یا فیبروئید) تومورهای خوش‌خیم و تک کلونی سلول‌های عضله‌ی صاف دیواره‌ی رحم می‌باشند. ترومبو آمبولی وریدی (VTE یا Venous thromboembolism) از عوارض شایع سرطان است؛ با این حال، سهم عوامل ترومبوتیک در بیماران مبتلا به سرطان نتایج متناقضی دارد. مطالعه‌ی حاضر به منظور بررسی ارتباط بین پلی‌مورفیسم ژن عوامل انعقادی و خطر ابتلا به میوم رحمی طراحی و اجرا شد.روش‌ها: در مطالعه‌ی حاضر، سه پلی‌مورفیسم ژن عامل انعقادی انتخاب شدند و با استفاده از روش ARMS-PCR (Amplification refractory mutation system- polymerase chain reaction) مورد بررسی قرار گرفتند. در این مطالعه، شیوع پلی‌مورفیسم‌های ژن پروترومبین (A20210G) (PTH یا Prothrombin)، بتا فیبرینوژن (A/G455) (FGB یا Fibrinogen beta) و بازدارنده‌ی فعال کننده‌ی پلاسمینوژن1 (G5/G4) (1-PAI یا 1-Plasminogen activator inhibitor) در 50 زن با تشخیص کلینیکی میوم رحمی و 50 زن سالم مورد بررسی قرار گرفتند. داده‌ها به وسیله‌ی نرم‌افزار SPSS نسخه‌ی 19 و با کمک آزمون 2χ تجزیه و تحلیل شدند.یافته‌ها: پلی‌مورفیسم‌های (1799963rs) PTH، (1800790rs) FGB و (1799889rs) 1-PAI با افزایش خطر ابتلا به میوم رحمی در جامعه‌ی مورد مطالعه، ارتباط معنی‌داری نداشتند (050/0 < P).نتیجه‌گیری: هیچ ارتباطی بین پلی‌مورفیسم‌های مورد بررسی و خطر ابتلا به میوم رحمی مشاهده نشد.

کلیدواژه‌ها

عنوان مقاله [English]

The Association of Thrombosis-Related Factors Polymorphisms and the Risk of Uterine Myoma

نویسندگان [English]

Mohadeseh Arabnejad ¹
Ahmad Ebrahimi ²
Mahboobeh Nasiri ³
Mehran Karimi ⁴

¹ Department of Biology, Islamic Azad University, Arsanjan Branch, Arsanjan, Iran

² Assistant Professor, Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran

³ Assistant Professor, Department of Biology, Islamic Azad University, Arsanjan Branch, Arsanjan, Iran

⁴ Associate Professor, Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

چکیده [English]

Background: Myomas are benign monoclonal tumors of the smooth muscle cells of the endometrium. Venous thromboembolism (VTE) is a common complication of cancers; however, their contributions to thrombotic tendency in patients with cancer have conflicting results. The present study was designed to investigate the relationship of the polymorphisms of clotting factor gene and the risk of uterine myoma.Methods: In this study, three selected polymorphisms of thrombotic factors gene were evaluated using amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) method. We focused on the prevalence of PTH G20210A, FGB G-455A and PAI-1 4G/5G polymorphisms in 50 women with clinically diagnosed uterine myoma and 50 healthy controls. The data were analyzed using chi-square test via SPSS19 software.Findings: The PTH (rs1799963), FGB (rs1800790) and PAI-1 (rs1799889) polymorphisms were not correlated with an increased risk of uterine myoma in the study population (P > 0.05).Conclusion: We observed no associations of the investigated polymorphisms with the risk of uterine myoma in studied population.

کلیدواژه‌ها [English]

Thrombosis factor
Uterine myoma
PTH G20210A
FGB G-455A
PAI-14G/5G

مراجع

Young A, Chapman O, Connor C, Poole C, Rose P, Kakkar AK. Thrombosis and cancer. Nat Rev Clin Oncol 2012; 9(8): 437-49.
Heit JA, Silverstein MD, Mohr DN, Petterson TM, O'Fallon WM, Melton LJ, III. Risk factors for deep vein thrombosis and pulmonary embolism: a population-based case-control study. Arch Intern Med 2000; 160(6): 809-15.
Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood 2002; 100(10): 3484-8.
Blom JW, Vanderschoot JP, Oostindier MJ, Osanto S, van der Meer FJ, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost 2006; 4(3): 529-35.
Borsig L. The role of platelet activation in tumor metastasis. Expert Rev Anticancer Ther 2008; 8(8): 1247-55.
Staton CA, Brown NJ, Lewis CE. The role of fibrinogen and related fragments in tumour angiogenesis and metastasis. Expert Opin Biol Ther 2003; 3(7): 1105-20.
Maly J, Blazek M, Blaha M, Pecka M. [Changes in hemostasis in malignant diseases]. Vnitr Lek 2002; 48(7): 614-8.
Nash GF, Turner LF, Scully MF, Kakkar AK. Platelets and cancer. Lancet Oncol 2002; 3(7): 425-30.
Gay LJ, Felding-Habermann B. Contribution of platelets to tumour metastasis. Nat Rev Cancer 2011; 11(2): 123-34.
Palumbo JS, Kombrinck KW, Drew AF, Grimes TS, Kiser JH, Degen JL, et al. Fibrinogen is an important determinant of the metastatic potential of circulating tumor cells. Blood 2000; 96(10): 3302-9.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Platelets and fibrin(ogen) increase metastatic potential by impeding natural killer cell-mediated elimination of tumor cells. Blood 2005; 105(1): 178-85.
Palumbo JS, Talmage KE, Massari JV, La Jeunesse CM, Flick MJ, Kombrinck KW, et al. Tumor cell-associated tissue factor and circulating hemostatic factors cooperate to increase metastatic potential through natural killer cell-dependent and-independent mechanisms. Blood 2007; 110(1): 133-41.
Palumbo JS, Talmage KE, Liu H, La Jeunesse CM, Witte DP, Degen JL. Plasminogen supports tumor growth through a fibrinogen-dependent mechanism linked to vascular patency. Blood 2003; 102(8): 2819-27.
Camerer E, Qazi AA, Duong DN, Cornelissen I, Advincula R, Coughlin SR. Platelets, protease-activated receptors, and fibrinogen in hematogenous metastasis. Blood 2004; 104(2): 397-401.
Im JH, Fu W, Wang H, Bhatia SK, Hammer DA, Kowalska MA, et al. Coagulation facilitates tumor cell spreading in the pulmonary vasculature during early metastatic colony formation. Cancer Res 2004; 64(23): 8613-9.
Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M, Nallari P. The genetic bases of uterine fibroids; a review. J Reprod Infertil 2011; 12(3): 181-91.
Lee EJ, Kong G, Lee SH, Rho SB, Park CS, Kim BG, et al. Profiling of differentially expressed genes in human uterine leiomyomas. Int J Gynecol Cancer 2005; 15(1): 146-54.
Poort SR, Rosendaal FR, Reitsma PH, Bertina RM. A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood 1996; 88(10): 3698-703.
Rey E, Kahn SR, David M, Shrier I. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet 2003; 361(9361): 901-8.
Rupert JL, Monsalve MV, Kidd KK, Tan C, Hochachka PW, Devine DV. Selective pressure has not acted against hypercoagulability alleles in high-altitude Amerindians. Ann Hum Genet 2003; 67(Pt 5): 426-32.
Thomas AE, Green FR, Kelleher CH, Wilkes HC, Brennan PJ, Meade TW, et al. Variation in the promoter region of the beta fibrinogen gene is associated with plasma fibrinogen levels in smokers and non-smokers. Thromb Haemost 1991; 65(5): 487-90.
Dawson SJ, Wiman B, Hamsten A, Green F, Humphries S, Henney AM. The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells. J Biol Chem 1993; 268(15): 10739-45.
Xu X, Xie Y, Lin Y, Xu X, Zhu Y, Mao Y, et al. PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis. Exp Ther Med 2012; 4(6): 1127-33.
Sartori MT, Wiman B, Vettore S, Dazzi F, Girolami A, Patrassi GM. 4G/5G polymorphism of PAI-1 gene promoter and fibrinolytic capacity in patients with deep vein thrombosis. Thromb Haemost 1998; 80(6): 956-60.
Hartmann KE, Birnbaum H, Ben-Hamadi R, Wu EQ, Farrell MH, Spalding J, et al. Annual costs associated with diagnosis of uterine leiomyomata. Obstet Gynecol 2006; 108(4): 930-7.
Marshburn PB, Matthews ML, Hurst BS. Uterine artery embolization as a treatment option for uterine myomas. Obstet Gynecol Clin North Am 2006; 33(1): 125-44.
Eroglu A, Egin Y, Cam R, Akar N. The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis. Ann Hematol 2009; 88(1): 73-6.
Vairaktaris E, Yapijakis C, Wiltfang J, Ries J, Vylliotis A, Derka S, et al. Are factor V and prothrombin mutations associated with increased risk of oral cancer? Anticancer Res 2005; 25(3c): 2561-5.
Blasiak J, Smolarz B. Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is not associated with breast cancer. Acta Biochim Pol 2000; 47(1): 191-9.
Gilabert-Estelles J, Ramon LA, Braza-Boils A, Gilabert J, Chirivella M, Espana F, et al. Plasminogen activator inhibitor-1 (PAI-1) 4 G/5 G polymorphism and endometrial cancer. Influence of PAI-1 polymorphism on tissue PAI-1 antigen and mRNA expression and tumor severity. Thromb Res 2012; 130(2): 242-7.
Lee JH, Ryu KW, Kim S, Bae JM. Preoperative plasma fibrinogen levels in gastric cancer patients correlate with extent of tumor. Hepatogastroenterology 2004; 51(60): 1860-3.
Yamashita H, Kitayama J, Kanno N, Yatomi Y, Nagawa H. Hyperfibrinogenemia is associated with lymphatic as well as hematogenous metastasis and worse clinical outcome in T2 gastric cancer. BMC Cancer 2006; 6: 147.
Yamashita H, Kitayama J, Nagawa H. Hyperfibrinogenemia is a useful predictor for lymphatic metastasis in human gastric cancer. Jpn J Clin Oncol 2005; 35(10): 595-600.
Takeuchi H, Ikeuchi S, Kitagawa Y, Shimada A, Oishi T, Isobe Y, et al. Pretreatment plasma fibrinogen level correlates with tumor progression and metastasis in patients with squamous cell carcinoma of the esophagus. J Gastroenterol Hepatol 2007; 22(12): 2222-7.
Jones JM, McGonigle NC, McAnespie M, Cran GW, Graham AN. Plasma fibrinogen and serum C-reactive protein are associated with non-small cell lung cancer. Lung Cancer 2006; 53(1): 97-101.
von Tempelhoff GF, Nieman F, Heilmann L, Hommel G. Association between blood rheology, thrombosis and cancer survival in patients with gynecologic malignancy. Clin Hemorheol Microcirc 2000; 22(2): 107-30.