TABLE 1.

Summary of reported outcomes in the studies included

Reference	Study design	Study population and age (average/range)	Results Summary: gene selection process	Analytical Methods used
O’reilly et al,22 2002	Case control	20 female patients 35 to 75 y old (mean age, 51.8 y) diagnosed with detrusor instability. 20 age- and sex-matched controls 35 to 71 y old (mean age, 53.6 y) were recruited, in whom urodynamics showed a stable bladder.	Quantitative RT-PCR reveals significantly decreased P2X1, P2X4, and P2X7 expression but significantly increased P2X2 expression in idiopathic detrusor instability bladders. As only P2X2 expression is increased in idiopathic detrusor instability bladders, it strongly implies that a P2X1 or P2X2 heteromultimer is crucial for the changes in purinergic innervation in idiopathic detrusor instability bladders.	Immunohistochemistry Quantitative RT-PCR
Maake et al,23 2006	Case control	Detrusor samples of 13 OABs (sensory urge and detrusor instability) were obtained before botulinum toxin injection and compared with those of 8 normally contractile, no obstructed bladders obtained during radical cystectomy.	In the smooth muscle of patients with detrusor instability and sensory urge, a significant 2.4- and 2.2-fold increase, respectively, in SMTN variant 1 messenger RNA was observed compared with that of normal controls. Analyses at the SMTN protein level confirmed significant up-regulation in these bladder dysfunctions by a factor of 2.3 and 1.8, respectively. No significant difference in SMTN expression was observed between detrusor instability and sensory urge.	Northern blot Quantitative RT-PCR Immunohistochemistry
Moore et al,24 2001	Case control	Detrusor samples were taken from: controls, at cystectomy for cancer or cystoscopic biopsy for hematuria (n=22; age, 33–88 y), child bladder, at surgical correction of vesicoureteral reflux (n=21; age 4 mo to 2 y), and adults with detrusor instability at cystoscopy-cystodistension (n=18; age 30–81 y).	The lack of P2X3 and P2X5 may impair control of detrusor contractility and contribute to the pathophysiology of urge incontinence.	Immunohistochemistry
Schofield et al,25 2005	Case control	A series of 18 women with urodynamically proven detrusor instability (median age, 62 y; range, 39–85 y), who were refractory to treatment, underwent cystoscopy and cold cup biopsy. Controls (n=26; median age, 65 y) were females without urgency or urge incontinence, undergoing cystoscopy for other indications.	The increase in GAP43 with age and with previous cystitis history suggests that neuronal sprouting is important in some subsets of patients with idiopathic detrusor instability.	Immunohistochemistry
Mukerji et al,26 2006	Case control	Bladder specimens obtained from patients with PBS (n=16), detrusor overactivity (n=14), and asymptomatic microscopic hematuria (controls, 17).	There was marked increase of TRPM8-immunoreactive nerve fibers in IDO (P=.0249) and PBS (P<.0001) specimens, compared with controls. A significantly higher number of TRPM8-immunoreactive axons were also seen in the IDO (P=.0246) and PBS (P<.0001) groups. Urothelial TRPM8 and TRPM8-immunoreactive thick myelinated fibers seemed unchanged in IDO and PBS.	Immunohistochemistry
Roosen et al,27 2009	Case control	32 patients with OAB and refractory detrusor overactivity, and 8 controls without lower urinary tract symptoms underwent cystoscopic bladder biopsy.	Significant 2-fold up-regulation of cadherin-11 was found in the suburothelium of patients with OAB compared with that in controls (P=.018), whereas β-catenin was similar in the groups (P=.6).	Quantitative immunohistochemistry
Neuhaus et al,28 2005	Case control	Control tissue samples were taken from the bladder dome, excluding the trigonal area, at cystectomies or as biopsies during transurethral tumor resections (5 women: mean age, 65 y; SD, 10.5; range, 54–81; 6 men: 73.5 y; SD, 5.7; range, 64–80.	Semiquantitative analyses showed significantly higher Cx43 expression in the detrusor muscle and a tendency to higher Cx45 expression in the suburothelial layer associated with urge symptoms, whereas Cx40 expression was unaffected.	Indirect immunofluorescence
Roberts et al,29 2020	Case control	Samples from patients with no symptoms of OAB (non-OAB cohort: age, 72.0±2.3 y) and those from patients with symptoms of OAB (clinical diagnosis, frequency ≥8/d, urgency with or without urgency incontinence), diagnosed with IDO (OAB with no neurologic abnormality, OAB cohort: age, 60.0± 5.0 y) were collected.	OABs exhibited greater TRPV4-induced ATP release with age dependence. These data provide the first evidence in humans for the key functional role of TRPV4 in urothelium with specific mechanisms and identify TRPV4 up-regulation in aging and OABs	Western blotting
Mukerji et al,30 2006	Case control	Bladder specimens were obtained from patients with detrusor overactivity (n=12) and controls with asymptomatic microscopic hematuria (n=16).	Muscarinic receptor subtypes 2 and 3 immunoreactivity significantly correlated with the urgency score (P=.0002 and P=.0206, respectively) and muscarinic receptor subtype 2 immunoreactivity correlated with the frequency score (P=.0029).	Immunohistochemistry

ATP, adenosine triphosphate; GAP43, growth-associated protein 43; IDO, idiopathic detrusor overactivity; OAB, overactive bladder; P2X, purinergic receptor P2X; PBS, painful bladder syndrome; RT-PCR, reverse transcriptase-polymerase chain reaction; SMTN, smoothelin; TRPM8, transient receptor potential cation channel subfamily M member 8; TRPV4, transient receptor potential cation channel subfamily V member 4.