Systematic review and metaanalysis of genetic association studies of urinary symptoms and prolapse in women

被引：87

作者：

Cartwright, Rufus ^{[1
,2
,3
]}

Kirby, Anna C. ^{[12
,13
]}

Tikkinen, Kari A. O. ^{[14
,15
,16
,20
]}

Mangera, Altaf ^{[9
]}

Thiagamoorthy, Gans ^{[7
]}

Rajan, Prabhakar ^{[11
]}

Pesonen, Jori ^{[17
]}

Ambrose, Chris ^{[8
]}

Gonzalez-Maffe, Juan ^{[5
]}

Bennett, Phillip ^{[6
]}

Palmer, Tom ^{[10
]}

Walley, Andrew ^{[4
]}

Jaervelin, Marjo-Riitta ^{[1
,2
,18
,19
]}

Chapple, Chris ^{[9
]}

Khullar, Vik ^{[3
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol, London SW7 2AZ, England

[2] Univ London Imperial Coll Sci Technol & Med, Dept Biostat, London SW7 2AZ, England

[3] Univ London Imperial Coll Sci Technol & Med, Dept Urogynecol, London SW7 2AZ, England

[4] Univ London Imperial Coll Sci Technol & Med, Dept Genom Common Dis & Mol Genet & Genom, London SW7 2AZ, England

[5] Univ London Imperial Coll Sci Technol & Med, Clin Trials Unit, London SW7 2AZ, England

[6] Univ London Imperial Coll Sci Technol & Med, Inst Reprod & Dev Biol, London SW7 2AZ, England

[7] Kings Coll London, Dept Urogynecol, London, England

[8] UCL, Sch Med, London W1N 8AA, England

[9] Univ Sheffield, Dept Urol Res, Sheffield, S Yorkshire, England

[10] Univ Warwick, Warwick Med Sch, Div Hlth Sci, Coventry CV4 7AL, W Midlands, England

[11] Univ Glasgow, Beatson Inst Canc Res, Glasgow, Lanark, Scotland

[12] Univ Calif San Diego, Dept Reprod Med, San Diego, CA 92103 USA

[13] Kaiser Permanente, Dept Obstet & Gynecol, San Diego, CA USA

[14] Univ Helsinki, Cent Hosp, Dept Urol, Helsinki, Finland

[15] Univ Helsinki, Cent Hosp, Dept Publ Hlth, Helsinki, Finland

[16] Univ Helsinki, Helsinki, Finland

[17] Univ Tampere, Dept Urol, FIN-33101 Tampere, Finland

[18] Univ Oulu, Inst Hlth Sci, SF-90100 Oulu, Finland

[19] Univ Oulu, Bioctr Oulu, SF-90100 Oulu, Finland

[20] McMaster Univ, Dept Clin Epidemiol & Biostat, Hamilton, ON, Canada

来源：

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY | 2015年 / 212卷 / 02期

关键词：

genetics; incontinence; lower urinary tract symptoms; overactive bladder; prolapse; systematic review; PELVIC ORGAN PROLAPSE; SP1-BINDING SITE POLYMORPHISM; RISK-FACTORS; BETA(3)-ADRENOCEPTOR AGONIST; ALPHA-1; POLYMORPHISM; FLOOR DISORDERS; TRACT SYMPTOMS; INCONTINENCE; PREVALENCE; SUSCEPTIBILITY;

D O I：

10.1016/j.ajog.2014.08.005

中图分类号：

R71 [妇产科学];

学科分类号：

100211 ;

摘要：

OBJECTIVE: Family studies and twin studies demonstrate that lower urinary tract symptoms and pelvic organ prolapse are heritable. This review aimed to identify genetic polymorphisms tested for an association with lower urinary tract symptoms or prolapse, and to assess the strength, consistency, and risk of bias among reported associations. STUDY DESIGN: PubMed and HuGE Navigator were searched up to May 1, 2014, using a combination of genetic and phenotype key words, including " nocturia," " incontinence," " overactive bladder," " prolapse," and " enuresis." Major genetics, urology, and gynecology conference abstracts were searched from 2005 through 2013. We screened 889 abstracts, and retrieved 78 full texts. In all, 27 published and 7 unpublished studies provided data on polymorphisms in or near 32 different genes. Fixed and random effects metaanalyses were conducted using codominant models of inheritance. We assessed the credibility of pooled associations using the interim Venice criteria. RESULTS: In pooled analysis, the rs4994 polymorphism of the ADRB3 gene was associated with overactive bladder ( odds ratio [ OR], 2.5; 95% confidence interval [ CI], 1.7e3.6; n 419). The rs1800012 polymorphism of the COL1A1 gene was associated with prolapse ( OR, 1.3; 95% CI, 1.0e1.7; n 838) and stress urinary incontinence ( OR, 2.1; 95% CI, 1.4e3.2; n 190). Other metaanalyses, including those for polymorphisms of COL3A1, LAMC1, MMP1, MMP3, and MMP9 did not show significant effects. Many studies were at high risk of bias from genotyping error or population stratification. CONCLUSION: These metaanalyses provide moderate epidemiological credibility for associations of variation in ADRB3 with overactive bladder, and variation of COL1A1 with prolapse. Clinical testing for any of these polymorphisms cannot be recommended based on current evidence. Key words: genetics, incontinence, lower urinary tract symptoms, overactive bladder, prolapse, systematic review

引用

页码：199.e1 / 199.e24

页数：24

共 80 条

[1] Effects of Mirabegron, a Novel β3-Adrenoceptor Agonist, on Primary Bladder Afferent Activity and Bladder Microcontractions in Rats Compared With the Effects of Oxybutynin [J].