The Relationship of Polymorphism of LYSYL Oxidase Like-1 Gene and Pelvic Organ Prolapse in Balinese Women

Abstract

Background: Pelvic organ prolapse (POP) data from Sanglah General Hospital Bali revealed proportion of 91.2% Balinese women, and that proportion was not decreased even with modification of workload and contraception. One of the associated factor is the decrease of expression of elastin and proteins involved in elastin metabolism, such as lysyl oxidase-like 1 (LOXL-1). There is genetic factor in the pathogenesis of prolapse, and polymorphism of elastogenesis-related gene, such as LOXL1 gene, associated with elastinopathy. Methods: We conducted an observational case control study in Balinese women population. Balinese women are women who have lineage of at least 3 generations (from grandparents) from Balinese people. Thirty patients with prolapse were taken as cases and 30 patients non prolapse as controls. DNA was isolated from venous blood, and then LOXL1 gene amplificated by polymerase chain reaction and then electrophoresis, and finally the DNA products were sequenced. Data was analyzed wih SPSS 21.0 for Windows. To determine whether the LOXL1 gene polymorphism is a risk factor for POP, a Chi-Square test was performed, and then variables were controlled by multivariate analysis using conditional logistic regression tests. Results: From the distribution of polymorphism, there were 13 samples in the case group (43.34% of the case group), compared to 5 samples in the control group (16.67% of the control group), and for the distribution of non-polymorphism, there were 17 samples in the case group (56.66% of the case group), compared to 25 samples in the control group (83.33% of the control group). From the analysis of polymorphism of LOXL1 gene rs2304719 in Balinese women, we found OR 3.824, CI 95% 1.150-12.713, p = 0.024). The LOXL1 gene polymorphism remains a risk factor for prolapse occurrence after the control variables were controlled by multivariate analysis using conditional logistic regression tests. The LOXL1 gene polymorphism, after the four control variables were controlled, gave a risk for prolapse incidence of 3,791 times by multivariate analysis (adjusted OR = 3.791; 95% CI = 1.065-13.496; p = 0.04). Conclusion: Polymorphism of LOXL1 gene rs2304719 is a risk factor for prolapse in Balinese women. Study for other gene polymorphisms are needed, before we can make a multigene panel testing for risk assessment. We hope in the future, multigene panel testing will be simpler, easier and cheaper, so that women at risk can be identified, and then can be informed and advised to avoid or reduce risk factors for prolapse. Keywords: DNA sequencing, elastinogenesis, elastinopathy, fibroblast, genetic factor of prolapse, multigene panel testing, polymerase chain reaction, uterosacral ligament