Pelvic organ prolapse (POP) is a common disease in older and middle-aged women and is mainly caused by age, obesity, and parity. Women who suffer from POP can experience discomfort, pain voiding disorder, and walking difficulty and have a considerable decrease in their quality of life. Due to reports on POP between mother and daughter and in women who have not acquired risk factors for POP (i.e., nulliparity), researchers have associated primary POP with specific genetic risk factors in European and American populations. Estrogen deficiency and collagen abnormalities are two risk factors for POP. Collagen is one of the main structures of the connective tissue and comes in several types, type I and type III being the most common. Type III collagen is found in the vaginal wall and surrounding pelvic organs. According to previous meta-analyses in European populations, the polymorphism of collagen type III α-1 (COL3A1) rs1800255 (genotype AA) is associated with POP(1). However, there have been few reports regarding the association between POP and collagen polymorphisms in Asian women. Thus, we aimed to study whether COL3A1 rs1800255 polymorphism was associated with POP in Japanese women.

A total of 40 women with pelvic organ prolapse quantification (POP-Q) stage III or IV were included in this study. A control group of 17 women without POP was also included. Peripheral blood samples were collected from each woman, and DNA was extracted using a genomic DNA kit. The primers and probe used in the assay were chosen at the Applied Biosystems . Single nucleotide gene polymorphisms (SNPs) in COL3A1 rs1800255 were ascertained by TaqMan real-time polymerase chain reaction and discriminated by genotyping assay. In each sample, 5 µL (10 ng) of DNA was reacted. We compared the proportion of COL3A1 genotype AA, AG, and GG between the POP and control groups. Participant characteristics (e.g., age, body mass index, and parity status) were compared between the groups by Student’s t-test. Due to the small number of participants, we did not compare the frequency of significant SNPs between the groups. A p-value of <0.05 was considered statistically significant.

The average age in the POP group was significantly higher than that in the control group (70.0 and 63.3 years old, respectively; P=0.0112). There was no significant difference in body mass index between the two groups (24.8 kg/m2 in the POP group and 24.0 kg/m2 in the control group). Parity tended to be higher in the POP group than in the control group (P=0.09). The prevalence of each genotype rs1800255 polymorphism in COL3A1 was 10% for AA, 45% for AG, and 45% for GG in the POP group. In addition, there was little difference between POP-Q stage III (9.1% for AA, 40.9% for AG, and 50.0% for GG) and POP-Q stage IV (11.1% for AA, 50.0% for AG, and 38.9% for GG). The prevalence of genotype polymorphisms in the control group was 17.6% for AA, 52.9% for AG, and 29.4% for GG.

Although parity tended to be higher in the POP group than in the control group (P=0.09), the proportion of each genotype of rs1800255 in the POP group was similar to the reported genotype frequency of rs1800255 in Japanese people. In addition, there was no correlation between the presence of genotype AA (risk factor) and severity of POP. These results suggest that the polymorphism of COL3A1 is not related to the onset and severity of POP in Japanese women.

The results indicate that the COL3A1 rs1800255 polymorphism has no association with POP in Japanese women. However, due to genetic differences in different world populations, further studies are needed to clarify the association of genomic polymorphisms with POP(2). The knowledge of acquired risk factors and genomic background in patients with POP is required to help improve surgical indications and prevent POP by earlier treatments.

Genetic epidemiology of pelvic organ prolapse: a systematic review. Am J Obstet Gynecol. Oct;211(4): 326-335, 2014.
Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women. Am J Obstet Gynecol. Feb;212(2):199.e1-24, 2015.