The predictive role of toll-like receptor-4 genetic polymorphisms in susceptibility to and prognosis of prostatic hyperplasia

Document Type: Original Article

Authors

Department of General Surgery, Pudong Branch of Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P.R. China

Abstract

Objective(s): This study was aimed to evaluate whether single nucleotide polymorphisms (SNPs) of TLR4 and common living habits of prostate hyperplasia (BPH) patients would affect the subjects’ risk and prognosis.
Materials and Methods: We totally recruited 501 BPH patients and 964 healthy controls. The patients’ international prostate symptom score (IPSS) and quality of life assessment (QoL) were designated as the prognostic indexes for BPH patients. Altogether 7 SNPs within TLR4 were selected, and the interactions among SNPs and living habits were explained with multi-factor dimensionality reduction (MDR) modeling.
Results: The mutant alleles of rs10983755 (G>A) and rs1927907 (G>A) tended to put on risk of BPH, yet the wide alleles of rs4986791 (C>T) and rs115336889 (G>C) were associated with incremental susceptibility to BPH (P<0.05). The rs10983755 (GA) and rs1927907 (GA) were suggested as the marker of non-aggressive BPH, whereas rs4986791 (TT) could symbolize aggressive BPH (P<0.05). The homozygotes of rs4986791 (TT) and rs115336889 (CC) could improve the IPSS change, and rs115336889 (CC) was also correlated with more obviously ameliorated Qol change (P<0.05). Finally, MDR modeling suggested that rs4986791 (TT) and rs115336889 (GG) shaped the genotyping combination featured by the lowest risk of BPH when smoking or drinking history was also evaluated.
Conclusion: The SNPs situated within TLR4 were potent candidates for predicting risk and prognosis of BPH patients, and their interactions within environmental parameters also helped to develop effective strategies for preventing and treating BPH.

Keywords

Main Subjects


1. Ronningen LD. Campbell’s urology, 8th ed. J Urol 2005; 173:326-326.
2. Berry SJ, Coffey DS, Walsh PC, Ewing LL. The development of human benign prostatic hyperplasia with age. J Urol 1984; 132:474-479.
3. Acton JN, Salfinger SG, Tan J, Cohen PA. Outcomes of Total Laparoscopic Hysterectomy Using a 5-mm Versus 10-mm Laparoscope: A Randomized Control Trial. J Minim Invasive Gynecol 2016; 23:101-106.
4. Saraav I, Singh S, Sharma S. Outcome of Mycobacterium tuberculosis and Toll-like receptor interaction: immune response or immune evasion? Immunol Cell Biol 2014; 92:741-746.
5. O’Neill LA, Golenbock D, Bowie AG. The history of Toll-like receptors - redefining innate immunity. Nat Rev Immunol 2013; 13:453-460.
6. Makinen LK, Atula T, Hayry V, Jouhi L, Datta N, Lehtonen S, et al. Predictive role of Toll-like receptors 2, 4, and 9 in oral tongue squamous cell carcinoma. Oral Oncol 2015; 51:96-102.
7. van Beijnum JR, Buurman WA, Griffioen AW. Convergence and amplification of toll-like receptor (TLR) and receptor for advanced glycation end products (RAGE) signaling pathways via high mobility group B1 (HMGB1). Angiogenesis 2008; 11:91-99.
8. Jerrard-Dunne P, Sitzer M, Risley P, Buehler A, von Kegler S, Markus HS. Inflammatory gene load is associated with enhanced inflammation and early carotid atherosclerosis in smokers. Stroke 2004; 35:2438-2443.
9. Kolz M, Baumert J, Muller M, Khuseyinova N, Klopp N, Thorand B, et al. Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol. BMC Med Genet 2008; 9:9-20.
10. Roehrborn CG. Pathology of benign prostatic hyperplasia. Int J Impot Res 2008; 20 Suppl 3:S11-18.
11. Moore JH. The ubiquitous nature of epistasis in determining susceptibility to common human diseases. Hum Hered 2003; 56:73-82.
12. Hahn LW, Ritchie MD, Moore JH. Multifactor dimensionality reduction software for detecting gene-gene and gene-environment interactions. Bioinformatics 2003; 19:376-382.
13. Lim CF, Buchan NC. Measurement of serum PSA as a predictor of symptoms scored on the IPSS for patients with benign prostatic hyperplasia. N Z Med J 2014; 127:17-24.
14. O’Sullivan M, Murphy C, Deasy C, Iohom G, Kiely EA, Shorten G. Effects of transurethral resection of prostate on the quality of life of patients with benign prostatic hyperplasia. J Am Coll Surg 2004; 198:394-403.
15. McConnell JD, Roehrborn CG, Bautista OM, Andriole GL, Jr., Dixon CM, Kusek JW, et al. The long-term effect of doxazosin, finasteride, and combination therapy on the clinical progression of benign prostatic hyperplasia. N Engl J Med 2003; 349:2387-2398.
16. Martin MU, Wesche H. Summary and comparison of the signaling mechanisms of the Toll/interleukin-1 receptor family. Biochim Biophys Acta 2002; 1592:265-280.
17. Sabroe I, Read RC, Whyte MK, Dockrell DH, Vogel SN, Dower SK. Toll-like receptors in health and disease: complex questions remain. J Immunol 2003; 171:1630-1635.
18. Hori M, Nishida K. Toll-like receptor signaling: defensive or offensive for the heart? Circ Res 2008; 102:137-139.
19. Miller YI, Viriyakosol S, Binder CJ, Feramisco JR, Kirkland TN, Witztum JL. Minimally modified LDL binds to CD14, induces macrophage spreading via TLR4/MD-2, and inhibits phagocytosis of apoptotic cells. J Biol Chem 2003; 278:1561-1568.
20. Parker LC, Prince LR, Sabroe I. Translational mini-review series on Toll-like receptors: networks regulated by Toll-like receptors mediate innate and adaptive immunity. Clin Exp Immunol 2007; 147:199-207.
21. Liu H, Komai-Koma M, Xu D, Liew FY. Toll-like receptor 2 signaling modulates the functions of CD4+ CD25+ regulatory T cells. Proc Natl Acad Sci U S A 2006; 103:7048-7053.
22. Xu D, Komai-Koma M, Liew FY. Expression and function of Toll-like receptor on T cells. Cell Immunol 2005; 233:85-89.
23. den Dekker WK, Cheng C, Pasterkamp G, Duckers HJ. Toll like receptor 4 in atherosclerosis and plaque destabilization. Atherosclerosis 2010; 209:314-320.
24. Petrick JL, Freedman ND, Demuth J, Yang B, Van Den Eeden SK, Engel LS, et al. Obesity, diabetes, serum glucose, and risk of primary liver cancer by birth cohort, race/ethnicity, and sex: Multiphasic health checkup study. Cancer Epidemiol 2016; 42:140-146.
25. Wild SH, Morling JR, McAllister DA, Kerssens J, Fischbacher C, Parkes J, et al. Type 2 diabetes and risk of hospital admission or death for chronic liver diseases. J Hepatol 2016; 64:1358-1364.
26. Lorenz E, Frees KL, Schwartz DA. Determination of the TLR4 genotype using allele-specific PCR. Biotechniques 2001; 31:22-24.
27. Rau HH, Hsu CY, Lin YA, Atique S, Fuad A, Wei LM, et al. Development of a web-based liver cancer prediction model for type II diabetes patients by using an artificial neural network. Comput Methods Programs Biomed 2016; 125:58-65.
28. Ferwerda B, Kibiki GS, Netea MG, Dolmans WM, van der Ven AJ. The toll-like receptor 4 Asp299Gly variant and tuberculosis susceptibility in HIV-infected patients in Tanzania. AIDS 2007; 21:1375-1377.
29. Pulido I, Leal M, Genebat M, Pacheco YM, Saez ME, Soriano-Sarabia N. The TLR4 ASP299GLY polymorphism is a risk factor for active tuberculosis in Caucasian HIV-infected patients. Curr HIV Res 2010; 8:253-258.
30. Najmi N, Kaur G, Sharma SK, Mehra NK. Human Toll-like receptor 4 polymorphisms TLR4 Asp299Gly and Thr399Ile influence susceptibility and severity of pulmonary tuberculosis in the Asian Indian population. Tissue Antigens 2010; 76:102-109.
31. Xue Y, Zhao ZQ, Wang HJ, Jin L, Liu CP, Wang Y, et al. Toll-like receptors 2 and 4 gene polymorphisms in a southeastern Chinese population with tuberculosis. Int J Immunogenet 2010; 37:135-138.
32. Marengo A, Rosso C, Bugianesi E. Liver Cancer: Connections with Obesity, Fatty Liver, and Cirrhosis. Annu Rev Med 2016; 67:103-117.
33. Raff EJ, Kakati D, Bloomer JR, Shoreibah M, Rasheed K, Singal AK. Diabetes Mellitus Predicts Occurrence of Cirrhosis and Hepatocellular Cancer in Alcoholic Liver and Non-alcoholic Fatty Liver Diseases. J Clin Transl Hepatol 2015; 3:9-16.
34. Yang Z, Zhou L, Wu LM, Lai MC, Xie HY, Zhang F, et al. Overexpression of long non-coding RNA HOTAIR predicts tumor recurrence in hepatocellular carcinoma patients following liver transplantation. Ann Surg Oncol 2011; 18:1243-1250.
35. Ritchie MD, Hahn LW, Roodi N, Bailey LR, Dupont WD, Parl FF, et al. Multifactor-dimensionality reduction reveals high-order interactions among estrogen-metabolism genes in sporadic breast cancer. Am J Hum Genet 2001; 69:138-147.
36. Rohrmann S, Crespo CJ, Weber JR, Smit E, Giovannucci E, Platz EA. Association of cigarette smoking, alcohol consumption and physical activity with lower urinary tract symptoms in older American men: findings from the third National Health And Nutrition Examination Survey. BJU Int 2005; 96:77-82.