Comprehensive analysis of LAMC1 genetic variants in advanced pelvic organ prolapse

Abstract

Objective: We sought to comprehensively evaluate the association of laminin gamma-1 (LAMC1) and advance pelvic organ prolapse.

Study design: We conducted a candidate gene association of patients (n = 239) with stages III-IV prolapse and controls (n = 197) with stages 0-I prolapse. We used a linkage disequilibrium (LD)-tagged approach to identify single-nucleotide polymorphisms (SNPs) in LAMC1 and focused on non-Hispanic white women to minimize population stratification. Additive and dominant multivariable logistic regression models were used to test for association between individual SNPs and advanced prolapse.

Results: Fourteen SNPs representing 99% coverage of LAMC1 were genotyped. There was no association between SNP rs10911193 and advanced prolapse (P = .34). However, there was a trend toward significance for SNPs rs1413390 (P = .11), rs20563 (P = .11), and rs20558 (P = .12).

Conclusion: Although we found that the previously reported LAMC1 SNP rs10911193 was not associated with nonfamilial prolapse, our results support further investigation of this candidate gene in the pathophysiology of prolapse.

Figure 1

The LAMC1 gene structure is displayed diagrammatically with exons represented as black discs. Genotyped SNPs are noted with arrows and are color coded as follows: coding-nonsynonymous (red); coding-synonymous (green); intronic (blue); and flanking (black). The bottom panel illustrates an LD graphic with r² values and squares without any value indicates perfect LD. LAMC1, laminin gamma-1; LD, linkage disequilibrium; SNP, single-nucleotide polymorphism.