Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Menopause. 2020 Feb;27(2):223-229. doi: 10.1097/GME.0000000000001448.
Pelvic organ prolapse (POP) is a common health issue that has a profound negative influence on women's quality of life. Genetic susceptibility to POP has been increasingly investigated. In this study, we assessed the single-nucleotide polymorphisms (SNPs) of six collagen-related genes (COL14A1, COL5A1, COL4A2, COL3A1, COL1A1, and COL18A1) and the genetic association with POP in Chinese women.
We performed a candidate gene association study of case women (n = 48) with stage III and IV prolapse and control women (n = 48) without prolapse. A target region sequencing approach was used to identify the SNPs in collagen-related genes. The association between SNPs and POP was examined by Fisher exact tests for unadjusted model and logistic regression analysis adjusted for delivery and pregnancy.
There was a significant association between COL14A1 SNPs (rs4870723, rs2305600, and rs2305598; P = 0.013, 0.019, and 0.028, respectively), a COL5A1 SNP (rs3827852; P = 0.016), and COL4A2 SNPs (rs76425569, rs388222, and rs2281968; P = 0.049 for the three, and rs445348, P = 0.040) and POP, respectively. Although there was no significant association between the COL3A1 SNP and POP, there was a trend toward significance for COL14A1 SNP (rs2305603), COL4A2 SNP (rs74941798), two COL1A1 SNPs (rs2586488 and rs2249492) and three COL18A1 SNPs (rs1050351, rs56335679, and rs55690336), and POP.
We are the first to evaluate the relationship between COL14A1, COL5A1, and COL4A2 polymorphisms and POP, besides COL3A1, COL1A1, and COL18A1, which have been reported previously. We found several candidate SNPs that were significantly associated with prolapse in Chinese women. Our results provide new evidence for further investigation of the involvement of these potential genes in the etiology of POP.
盆腔器官脱垂（POP）是一种常见的健康问题，对女性的生活质量有深远的负面影响。遗传易感性与 POP 的关系已得到越来越多的研究。在这项研究中，我们评估了六个胶原相关基因（COL14A1、COL5A1、COL4A2、COL3A1、COL1A1 和 COL18A1）的单核苷酸多态性（SNPs）与中国女性 POP 的遗传相关性。
我们对患有 III 期和 IV 期脱垂的病例女性（n=48）和无脱垂的对照女性（n=48）进行了候选基因关联研究。采用靶向区域测序方法鉴定胶原相关基因中的 SNPs。采用 Fisher 精确检验对未调整模型和校正分娩和妊娠的 logistic 回归分析进行 SNP 与 POP 之间的关联分析。
COL14A1 SNPs（rs4870723、rs2305600 和 rs2305598；P=0.013、0.019 和 0.028）、COL5A1 SNP（rs3827852；P=0.016）和 COL4A2 SNPs（rs76425569、rs388222 和 rs2281968；P=0.049）与 POP 显著相关，COL4A2 还有三个 SNPs（rs445348、P=0.040）。尽管 COL3A1 SNP 与 POP 无显著关联，但与 COL14A1 SNP（rs2305603）、COL4A2 SNP（rs74941798）、两个 COL1A1 SNPs（rs2586488 和 rs2249492）和三个 COL18A1 SNPs（rs1050351、rs56335679 和 rs55690336）与 POP 相关的趋势有统计学意义。
我们首次评估了 COL14A1、COL5A1 和 COL4A2 多态性与 POP 的关系，除了先前报道的 COL3A1、COL1A1 和 COL18A1 外。我们发现了几个与中国女性脱垂显著相关的候选 SNP。我们的研究结果为进一步研究这些潜在基因在 POP 病因中的作用提供了新的证据。
