Mutation Screen of LOXL1 in Patients With Female Pelvic Organ Prolapse

Abstract

Objectives The LOXL1 (lysyl oxidase-like 1) gene encodes a copper-dependent monoamine oxidase that catalyzes the deamination of a lysine residue in the crosslinking of tropoelastin monomers to form elastin. LOXL1-KO mice do not deposit normal elastic fibers in their genitourinary tract resulting in post-partum pelvic organ prolapse and lower urinary tract dysfunction with decreased bladder capacity and lower voiding pressure. We sought to identify which single nucleotide polymorphisms (SNPs) in the LOXL1 coding sequence play a role in female pelvic organ prolapse (FPOP). Methods A total of 66 patients were screened, 48 in the case group and 18 in the control group. The 7 exons of LOXL1 were evaluated for any polymorphisms. Results Three missense sequence changes (Arg141Leu, Gly153Asp, and Ser159Ala) and three silent mutations (Asp292Asp, Ala320Ala, and Ile521Ile) were identified. None of these polymorphisms were found to differ significantly in frequency in the case group compared to the control group. Conclusion Our findings do not support an association of any LOXL1 exonal SNPs with the diagnosis of FPOP.

Advancing our understanding of genetic risk factors and potential personalized strategies in pelvic organ prolapse: largest GWAS to date reveals 19 novel associated loci

“…Subsequently, diverse mouse and human studies have reiterated its involvement with prolapse (34)(35)(36)(37). Additionally, we further propose several candidate genes (EFEMP1, CHRDL2, ACADVL, PLA2G6) which reinforce the role of connective tissue molecular changes as a key process in the pathogenesis of POP (38,39).…”

“…Subsequently, diverse mouse and human studies have reiterated its involvement with prolapse (34)(35)(36)(37). Additionally, we further propose several candidate genes (EFEMP1, .…”

Common variants in LAMC1 confer risk for pelvic organ prolapse in Chinese population

“…The polymorphisms of LAMC1 gene have been reported to be associated with colorectal cancer, premature ovarian failure and Mayer-Rokitansky-Kuster-Hauser syndrome ( MRKHS ) [ 15 , 19 , 20 ]. Together with laminin, many kinds of proteins can synergize to maintain the pelvic support organization, involving collagens (I, II and III) [ 16 ], MMP family menbers which could cleave fibrillar collagen and denature peptides [ 21 ], LOXL1 [ 22 ] and so on. Based on the functions of these genes in POP development, we hypothesized that variants in these genes might be associated with POP risk.…”

Modern molecular genetic and biochemical predictors of genital prolapse (a review)

“…При участии белка ЭЦМ фибулина-5 происходит связывание тропоэластина и LOXL1, что стабилизирует внешнюю поверхность кле-точных стенок соединительной ткани и организует по-лимеры эластина в функциональные эластичные во-локна [22]. Показано, что сниженная экспрессия генов LOX, LOXL1 и LOXL3 может приводить к несостоя-тельности соединительной ткани и провоцировать раз-витие пролапса гениталий и прямой кишки [23].…”

“…Это нарушает процессы ассоциации с эластичными волокнами, ве-дет к их неправильной укладке в микрофибрилляр-ном каркасе и формированию синдрома «вялой ко-жи» (сutis laxa) и других эластопатий (эмфиземы, врожденной извитости дуги аорты и др.) [23,29].…”