Estrogen receptor alpha polymorphism is associated with pelvic organ prolapse risk

Abstract

Estrogen and estrogen receptors are known to play important roles in the pathophysiology of pelvic organ prolapse (POP). We investigated whether estrogen receptor alpha (ERalpha) gene polymorphisms were associated with POP risk by conducting a case-control association study in 88 women with POP and 153 women without POP. Genotypes of the ERalpha (ESR1) gene polymorphisms (rs17847075, rs2207647, rs2234693, rs3798577, and rs2228480) were determined by polymerase chain reaction, followed by restriction fragment length polymorphism analysis. There was significant difference between women with and those without POP in the distribution of the ESR1 rs2228480 genotypes evaluated. By using multivariable logistic regression, age and ESR1 rs2228480 genotype GA were significantly associated with POP risk. Although the sample size of women with POP studied is small, the present study shows that ERalpha genotype may be associated with POP risk.

Genetic epidemiology of pelvic organ prolapse: a systematic review

“…Of these articles, 21 pertained to the genetic epidemiology of POP (Figure 1). This included one GWAS(17), two linkage analyses(18,19) and 18 case-control candidate gene association studies(20–37) involving 10 candidate genes (collagen type 1 alpha 1 ( COL1A1 ) (n=5)(26–28,33,35), collagen type 3 alpha 1 ( COL3A1 ) (n=4)(20,30–32), laminin gamma-1 ( LAMC1 ) (n=3) (19,23,36), matrix metalloproteinase 9 ( MMP9 ) (n=3)(24,28,37), matrix metalloproteinases 1 and 3 ( MMP1 & 3 ) (n=2)(28,34), lysyl oxidase-like 1 ( LOXL1 ) (n=1)(29), estrogen receptor alpha ( ER α)(n=1)(21), estrogen receptor beta ( ER β)(n=1)(22), progesterone receptor (PGR) (n=1)(25) (Table 1). All studies were published in 2007 or later.…”

“…All studies were published in 2007 or later. Most had government(17,18,20,21,23,25,29,32–37) and/or university grant funding(20–22,24,25), 71% (15/21).…”

“…Studies looked at Asian (33.3%, 7/21) (20–22,24–26,30), European (23.8%, 5/21) (27,28,31,33,34) and U.S. Caucasian populations (23.8%, 5/21(17–19,36,37); two studies included sub-analyses of African Americans(23,29) and Brazilian white and non-white (9.5%, 2/21)(32,35) populations (Table 1). When reported, the mean or median age of prolapse cases ranged from 48 to 66 years(17,18,21–24,27–37) and mean or median age of controls ranged from 49 to 69 years (17,21–24,27–37). Age was similar between cases and controls for nine studies(17,26–31,33), had a discrepancy of ≥ 5 years for six studies (23,32,34–37), a discrepancy of ≥ 10 years for three studies(21,22,24) and markedly disparate proportions of younger and older women in two studies (study did not report mean or median ages)(20,25).…”

Increased microRNA-221/222 and decreased estrogen receptor α in the cervical portion of the uterosacral ligaments from women with pelvic organ prolapse

“…It is well known that polymorphisms in the ERα gene are associated with an increased risk of POP [18], and many studies have indicated that reduced ERα expression occurs in POP [12,13]; however, the mechanisms that regulate reduced ERα protein levels are not known. This study confirms the previous studies of reduced ER expression in POP [12,13], as we observed that ERα protein is also downregulated in the cervical portion of the uterosacral ligament of POP patients.…”

UVA-Photoactivated Riboflavin Treatment of Vaginal Cells Derived from Pelvic Organ Prolapse Cases

“…It is estimated that annual POP surgeries involve an expenditure of over USD 1 billion [2]. The etiologies of POP have been extensively reviewed [5,6,7,8], and current evidence suggests an important etiology of POP is the degradation of collagen in vaginal tissues [9,10]. Interestingly, strengthening collagen fibers by cross-linking in collagen types I, III and V has been achieved using combined riboflavin UVA (365-370 nm) photoactivation treatment in corneal repairs [11,12,13,14].…”