The Relationship Between COL3A1 Exon 31 Polymorphism and Pelvic Organ Prolapse

Abstract

COL3A1 exon 31 polymorphism may have a role in determining the risk of pelvic organ prolapse in women with risk factors such as aging, vaginal childbirth and hypoestrogenism.

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.…”

“…The prolapse phenotype was most commonly defined by POP-Q stages II-IV(20–25,28,29,33,37), although some studies were more stringent(17,18,26–28,30,32–36), and two studies did not define the prolapse phenotype(19,31). All of the case-control studies defined the control as POP-Q stage 0 or 0-I.…”

“…The GWAS(17) and both linkage analyses(18,19) were performed in families with a high rate of POP. All other studies were population based(20–25,28,30,31,36,37). 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).…”

“…All other studies were population based(20–25,28,30,31,36,37). 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).…”

Recent studies of genetic dysfunction in pelvic organ prolapse: The role of collagen defects

“…[57][58][59][60][61][62][63][64] Nucleotide polymorphisms in the COL3A1 genes are associated with prolapse, thus suggesting the role of defective collagen III in the genesis of prolapse. [57][58][59] Interestingly, type IV Ehlers-Danlos syndrome is due to mutations in the same COL3A1 gene. Patients with this condition are known to have abnormal collagen III, which causes fragile tissues and poor wound healing.…”