Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women

A Case-Control Study

Sarah St. Louis, Richard Scott, Christa Lewis, Charbel Salamon, Jennifer Pagnillo, Nathan Treff, Deanne Taylor, Patrick Culligan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Objective: 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).

Original languageEnglish (US)
Pages (from-to)726-730
Number of pages5
JournalJournal of Minimally Invasive Gynecology
Volume23
Issue number5
DOIs
StatePublished - Jul 1 2016
Externally publishedYes

Fingerprint

Prolapse
Case-Control Studies
Single Nucleotide Polymorphism
Exome
Mutation
Robotics
Genome
Genes
Genetic Research
Chromosomes, Human, Pair 5
Human Genome
Advisory Committees
Missense Mutation
Nonparametric Statistics
Glycine
Serine
Referral and Consultation
Software
Odds Ratio
Demography

All Science Journal Classification (ASJC) codes

  • Obstetrics and Gynecology

Cite this

St. Louis, Sarah ; Scott, Richard ; Lewis, Christa ; Salamon, Charbel ; Pagnillo, Jennifer ; Treff, Nathan ; Taylor, Deanne ; Culligan, Patrick. / Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women : A Case-Control Study. In: Journal of Minimally Invasive Gynecology. 2016 ; Vol. 23, No. 5. pp. 726-730.
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abstract = "Objective: 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).",
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Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women : A Case-Control Study. / St. Louis, Sarah; Scott, Richard; Lewis, Christa; Salamon, Charbel; Pagnillo, Jennifer; Treff, Nathan; Taylor, Deanne; Culligan, Patrick.

In: Journal of Minimally Invasive Gynecology, Vol. 23, No. 5, 01.07.2016, p. 726-730.

Research output: Contribution to journalArticle

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T1 - Genetic Mutation that May Contribute to Failure of Prolapse Surgery in White Women

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AU - St. Louis, Sarah

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N2 - Objective: 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).

AB - Objective: 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).

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