Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women: A Case-Control Study

详细信息    查看全文

• 作者：Sarah St. Louis ; MD^a ; ^{Sarah.St.Louis@atlantichealth.org" class="auth_mail" title="E-mail the corresponding author} ; Richard Scott ; MD^b ; Christa Lewis ; DO^a ; Charbel Salamon ; MD ; MS^a ; Jennifer Pagnillo ; BSN^a ; Nathan Treff ; PhD^b ; Deanne Taylor ; PhD^b ; Patrick Culligan ; MD^a
• 关键词：Genetics ; Prolapse ; Robotic sacrocolpopexy ; Surgical failure
• 刊名：Journal of Minimally Invasive Gynecology
• 出版年：2016
• 出版时间：July-August 2016
• 年：2016
• 卷：23
• 期：5
• 页码：726-730
• 全文大小：500 K

文摘

To identify a potential genetic basis for early failure after prolapse surgery.

Design

Case-control study (Canadian Task Force classification II).

Setting

This study was carried out in 1 academic community medical center referral practice, and all patients had surgery at 1 of 2 hospitals.

Patients

Ten women with early, multicompartment prolapse recurrence after robotic sacrocolpopexy compared with 40 control subjects with known success after the same procedure.

Interventions

Patients were treated with robotic sacrocolpopexy.

Measurements and Main Results

DNA was isolated and initially genotyped on a single nucleotide polymorphism (SNP) array to direct more detailed exome analyses. Exome sequences were mapped to the Human Genome Reference Sequence (GRCh37), and variants were compared between groups and to participants in the 1000 Genomes Project. Statistical analyses were performed using a software package commonly used in genetics research. TaqMan assay was used for verification, and p values were adjusted using the false discovery rate. Demographics of groups were compared using χ², Mann-Whitney U, and t tests. A SNP [rs171821] located near the ZFYVE16 gene was associated with patients but not control subjects, and the false discovery rate–adjusted p value was .046 (odds ratio, 45.2; 95% confidence interval, 5.06–403). Exome analyses of this gene yielded another SNP [rs249038 (G/A)] in 6 of 10 patients and none of the control subjects (p = .02). This SNP causes a heterozygous missense mutation of glycine to serine predicted to be deleterious by the Protein Variation Effect Analyzer and was also very rare among participants in the 1000 Genomes Project (p < .001).

Conclusions

Two SNPs located near the ZFYVE16 gene on chromosome 5 may have played a role in the early, multicompartment sacrocolpopexy failure experienced by our patients. (www.clinicaltrials.gov Identifier: NCT01614587).