Genetic epidemiology of pelvic organ prolapse: a systematic review.
Given current evidence supporting a genetic predisposition for pelvic organ prolapse, we conducted a systematic review of published literature on the genetic epidemiology of pelvic organ prolapse. Inclusion criteria were linkage studies, candidate gene association and genome-wide association studies in adult women published in English and indexed in PubMed through Dec. 2012, with no limit on date of publication. Methodology adhered to the PRISMA guidelines. Data were systematically extracted by 2 reviewers and graded by the Venice criteria for studies of genetic associations. A metaanalysis was performed on all single nucleotide polymorphisms evaluated by 2 or more studies with similar methodology. The metaanalysis suggests that collagen type 3 alpha 1 (COL3A1) rs1800255 genotype AA is associated with pelvic organ prolapse (odds ratio, 4.79; 95% confidence interval, 1.91-11.98; P = .001) compared with the reference genotype GG in populations of Asian and Dutch women. There was little evidence of heterogeneity for rs1800255 (P value for heterogeneity = .94; proportion of variance because of heterogeneity, I(2) = 0.00%). There was insufficient evidence to determine whether other single nucleotide polymorphisms evaluated by 2 or more papers were associated with pelvic organ prolapse. An association with pelvic organ prolapse was seen in individual studies for estrogen receptor alpha (ER-α) rs2228480 GA, COL3A1 exon 31, chromosome 9q21 (heterogeneity logarithm of the odds score 3.41) as well as 6 single nucleotide polymorphisms identified by a genome-wide association study. Overall, individual studies were of small sample size and often of poor quality. Future studies would benefit from more rigorous study design as outlined in the Venice recommendations.
Department of Obstetrics and Gynecology, Division of Female Pelvic Medicine and Reconstructive Surgery, Vanderbilt University Medical Center, Nashville, TN.
Renée M
RM
Ward
Department of Obstetrics and Gynecology, Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, TN; Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN.
Digna R
DR
Velez Edwards
Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN; Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN.
Todd
T
Edwards
Institute of Medicine and Public Health, Vanderbilt University Medical Center, Nashville, TN.
Ayush
A
Giri
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN.
Rebecca N
RN
Jerome
Department of Obstetrics and Gynecology, Division of Urogynecology, University of North Carolina, Chapel Hill, NC.
Jennifer M
JM
Wu
D024061:Collagen Type III / Q000235:genetics; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D014943:Global Health; D006801:Humans; D015233:Models, Statistical; D017720:Molecular Epidemiology; D016017:Odds Ratio; D056887:Pelvic Organ Prolapse / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
C439971:COL3A1 protein, human; D024061:Collagen Type III; D005819:Genetic Markers
genetic epidemiology; genome wide association study; pelvic organ prolapse; single nucleotide polymorphism