Authors: Brock Sheehan, Bryson Edwards, Ivanna Soto, Justice Vance, Tyler Haywood, Jefferey Goddard, Logan Seegmiller, Mohammed A. El Saidi, Wissam R Zaidan , Asmahan El-Ezzi , Dr. Ruhul Kuddus
Mentors: Dr. Ruhul Kuddus
Insitution: Utah Valley University
Association of Cyclooxygenase 1 (COX-1) rs4648298 and Cyclooxygenase 2 (COX-2) rs20417 Polymorphisms and Prostatic diseases Among Lebanese Males
Brock J Sheehan1*, Bryson Edwards1, Ivanna Soto Medrano1, Justin Vance1, Tyler Haywood1, Jeffrey Goddard1, Logan Seegmiller1, Mohammed A. El Saidi2, Wissam R. Zaidan3, Asmahan A. El-Ezzi3, 4, Ruhul Kuddus1
1Department of Biology, 2Department of Strategic Management and Operations, Utah Valley University, Orem UT; 3Radioimmunoassay Laboratory, Lebanese Atomic Energy Commission, Beirut Lebanon; 4Department of Chemistry and Biochemistry, Lebanese University, Hadath, Lebanon. *- presenting author.
Background: COX-1 and COX-2 genes encode prostaglandin-endoperoxide synthases (PTGS) isoenzymes, involved in inflammation and possibly neoplasms. The genes are expressed in the prostate gland. Both genes have several polymorphisms. Here we examine the association of rs4648298 (A-G transition) and rs20417 (G-C transversion) polymorphisms and prostatic diseases. This research was approved by the Utah Valley University IRB.
Materials and Methods: DNA was extracted from a blood sample of 56 healthy volunteers, 51 volunteers with benign prostate hyperplasia (BPH), and 61 volunteers with clinical prostate cancer (PCa). Genotyping was conducted through PCR-RFLP analyses. The restriction enzymes used were BaeGI (for rs4648298) and AciI (rs20417), respectively. Alleles with the restriction site were considered recessive. The association was inferred through statistical analyses of the distribution of the genotypes (BB, Bb, and bb or AA, Aa and aa), and allele frequencies among the controls and the affected groups. A p-value of ≤0.05 was considered significant.
Results: The distribution of the genotypes is in Hardy-Weinberg equilibrium for all three groups. The b allele of the COX-1 gene is extremely rare (less than 3%), and no significant association between the B or b allele or BB, Bb, and bb genotypes and prostatic disease was observed. The a allele of the COX-2 gene is more common in the BPH group (p=0.011), but not the PCa group (p= 0.472) or the combined affected group (p=0.068) compared to the control group.
Conclusions: There is no association between the rs4648298 polymorphisms of the COX-1 gene and prostatic diseases. The a allele of the rs20417 polymorphisms of the COX-2 gene is associated with higher risks of BPH and possibly PCa. The small sample size, sampling from one ethnic group, and the low distribution of the b allele in the Lebanese population are limitations of this study.