. 2020 Sep 19;39(8):2089–2110. doi: 10.1002/nau.24512

Table 4.

Results of studies researching specific genes/proteins/product

Analyzed gene/protein/product	Study	Tissue^a	Result^b UUI	Control	p	Unit
AIP	Ustundag et al. (2019) ⁵⁰	Serum	0.048 ± 0.31	0.046 ± 0.26	.982	NI
Albumin	Ustundag et al. (2019) ⁵⁰	Serum	46 ± 10	55 ± 17	.151	g/L
Androgen receptor	Cornu et al. (2011) ¹⁴	Blood	AR polymorphism (combination of two alleles containing more than 21 CAG repeats) is significantly associated with UUI		.02	NA
AOPP	Keske et al. (2019) ³⁴	Serum	134.4 ± 32.6	138.9 ± 46.0	.641	NI
Arylesterase	Keske et al. (2019) ³⁴	Serum	184.6 ± 39.2	189.7 ± 55.7	.662	NI
ATP	Kumar et al. (2010) ³⁷	Urothelium	1064.2 ± 238.9	45.7 ± 4.9	NI	pmol/g
	Silva‐Ramos et al. (2013) ⁴⁹	Urine	27.5 ± 8.3	7.2 ± 1.7	.022	pM
B1‐integrin	Kanasaki et al. (2013) ²⁰	Mutated mice	B1‐KO mice exhibited UUI phenotype compared with controls. Urine spot number and spot area as a percentage of the filter paper area were significantly greater in the B1‐cKO mice; frequency distribution of urine spot volumes showed B1‐cKO mice had a greater proportion of urine deposits that were moderately large
B3‐AR	Honda et al. (2014) ¹⁶	Hair	Significantly higher frequency of variant Trp64Arg/Arg64Arg I in B3‐AR n OAB group versus controls. Within OAB‐group no significant difference in UUI pts with and without variant
BDNF	Alkis et al. (2017) ²⁷	Urine	844.3 ± 286.3	340.2 ± 199.0	NI	pg/mg
	Antunes‐Lopes et al. (2013) ²⁸	Urine	628.1 ± 590.5	110.4 ± 159.5	NI	pg/mg
	Richter et al. (2017)^c ^, ⁴⁷	Urine	62.0 ± 1.4	46.3 ± 1.2	NS difference	pg/mg
Calcium	Ustundag et al. (2019) ⁵⁰	Serum	Median [IQR]: 2.37 [0.12]	2.39 [0.07]	.724	mmol/L
CGRP	Richter et al. (2017)^c ^, ⁴⁷	Urine	595.5 ± 1.3	527.4 ± 1.5	NS difference	pg/mg
Cholesterol, total	Ustundag et al. (2019) ⁵⁰	Serum	5.58 ± 1.08	6.05 ± 1.13	.071	mmol/L
Collagenase I activity	Richter et al. (2017)^c ^, ⁴⁷	Urine	279.2 ± 449.0	138.9 ± 321.2	NS difference	µg/min/mg
CRP	Chuang et al. (2010) ³¹	Serum	2.96 ± 0.47	0.93 ± 0.27	.0002	mg/L
		Urine	All samples below assay sensitivity
	Hsiao et al. (2012) ³³	Serum	Median [IQR]: 0.12 [0.03–0.26]	0.055 [0.04–0.08]	.032	mg/dl
	Liu et al. (2013) ⁴⁵	Serum	0.33 ± 0.37	0.06 ± 0 0.04	.011	pg/ml
	Ustundag et al. (2019) ⁵⁰	Serum	Median [IQR]: 29.5 [0.9]	29.5 [0.9]	.994	nmol/L
(complementary) Dense plaques	Carey et al. (2000) ³⁰	Detrusor muscle	No apparent differences between the groups
CYP‐17 and CYP‐19	Cornu et al. (2011) ¹⁴	Blood	No significant difference in prevalence of polymorphisms between the groups
Estrogen receptor‐1	Cornu et al. (2011) ¹⁴	Blood	No significant difference in prevalence of polymorphisms between the groups
Disulfide	Ustundag et al. (2019) ⁵⁰	Serum	17.0 ± 4.2	19.0 ± 6.2	.118	µmol/L
FRAP	Ustundag et al. (2019) ⁵⁰	Serum	1135 ± 283	1120 ± 264	.842	µmol/L
GAG	Alkis et al. (2017) ²⁷	Urine	126.2 ± 45.1	90.9 ± 60.3	NI	pg/mg
GAP‐43	Schofield et al. (2005) ⁴⁸	PNT			NS difference	Area
GDNF	Antunes‐Lopes et al. (2013) ²⁸	Urine	958.1 ± 826.2	1.220.5 ± 513.5	.128	pg/mg
GMC‐SF	Richter et al. (2017)^c ^, ⁴⁷	Urine	All samples below assay sensitivity
Hba1c	Ustundag et al. (2019) ⁵⁰	Serum	Median [IQR]: 5.8 [0.5]	5.9 [0.7]	.363	%
HB‐EGF	Kim et al. (2015) ³⁵	Urine	9.4 ± 7.73	4.45 ± 2.93	NI	pg/mg
HDL	Ustundag et al. (2019) ⁵⁰	Serum	1.42 ± 0.43	1.42 ± 0.38	.835	mmol/L
HIF‐(1a/2a)	Christiaansen et al. (2011) ²⁴	HBUC	HIF‐1a: 20.06 ± 11.74%	HIF‐1a: 21.58 ± 12.39%	NS difference	%
HIF‐(1a/2a)	Christiaansen et al. (2011) ²⁴	HBUC	HIF2‐a: 13.7 ± 1.75%	HIF‐2a: 16.3 ± 3.15%	NS difference	%
IMA	Keske et al. (2019) ³⁴	Serum	0.614 ± 0.106	0.530 ± 0.117	.003	NI
	Ustundag et al. (2019) ⁵⁰	Serum	0.629 ± 0.257	0.569 ± 0.219	.335	Absorbance unit
Insulin	Liu et al. (2013) ⁴⁵	Serum	771.58 ± 502.54	759.8 ± 471.7	.922	pg/ml
Interleukins (IL‐1B, IL‐6, IL‐8)	Liu et al. (2013) ⁴⁵	Serum	IL‐Iβ: 4.68 ± 3.10	IL‐Iβ: 1.64 ± 2.37	.045	pg/ml
			IL‐6: 5.78 ± 9.97	IL‐6: 0.79 ± 1.05	.000
			IL‐8: 4.12 ± 3.81	IL‐8: 1.45 ± 1.06	.000
Richter et al. (2017)^c ^, ⁴⁷	Urine	IL‐6: 2.5 ± 1.5	IL‐6: 3.0 ± 1.1	NS difference	pg/mg
Richter et al. (2017)^c ^, ⁴⁷	Urine	IL‐8: 38.4 ± 1.1	IL‐8: 37.2 ± 1.3	NS difference	pg/mg
			IL‐1B below assay sensitivity
LDL	Ustundag et al. (2019) ⁵⁰	Serum	3.36 ± 1.00	3.7 ± 0.98	.089	mmol/L
Leptin	Liu et al. (2013) ⁴⁵	Serum	10,942 ± 14,338	6242 ± 4038	.922	pg/ml
MCP‐1	Alkis et al. (2017) ²⁷	Urine	635.7 ± 284.2	155.8 ± 79.4	NI	pg/mg
	Farhan et al. (2019) ³²	Urine	Mean: 209.25 ± (SEM) 30.5	48.02 ± 9	.001 (ANOVA control‐wet‐dry)	pg/mg
	Liu et al. (2013) ⁴⁵	Serum	132.46 ± 18.00	104.81 ± 37.39	.067	pg/ml
Membrane caveolae	Carey et al. (2000) ³⁰	Detrusor muscle	No apparent differences between the groups
MMP(‐1/2/9)	Richter et al. (2017)^c ^, ⁴⁷	Urine	MMP‐2: 251.8 ± 1.3	MMP‐2: 183.8 ± 1.5	NS difference	pg/mg
MMP(‐1/2/9)	Richter et al. (2017)^c ^, ⁴⁷	Urine	MMP‐9: 32.8 ± 1.9	MMP‐9: 28.2 ± 2.1	NS difference	ng/mg
			MMP‐1 below assay sensitivity
Muscarinic 2/3 receptor/M‐Ras	Birder et al. (2013) ²⁹	HBUC	Nonsignificant decrease of M3R‐expression in UUI group (shown in figure, exact data not shown)
Muscarinic 2/3 receptor/M‐Ras	Ehrhardt et al. (2015) ¹⁹	Mutated mice	M‐Ras^−/− male mice exhibited UUI phenotype. Dysregulation of M2R and M3R in M‐Ras^−/− mice; male mice had a higher expression of M2R, female mice lower expression M3R. Significantly more urine spots produced by M‐Ras^−/− males compared with WT males (p = .0124), while M‐Ras^−/− and WT females produced similar numbers of spots
NGF	Alkis et al. (2017) ²⁷	Urine	1107 ± 602.5	202.9 ± 48.4	NI	pg/mg
	Antunes‐Lopes et al. (2013) ²⁸	Urine	488.5 ± 591.8	188.3 ± 290.2	.005	pg/mg
	Kim et al. (2015) ³⁵	Urine	1.26 ± 1.07	0.5 ± 0.29	<.001	pg/mg
	Kuo et al. (2010) ³⁸	Urine	1.66 ± 3.30	0.09 ± 0.22	.015	pg/mg
	Kuo et al. (2010) ³⁹	Urine	1.83 ± 0.74	0.05 ± 0.02	.012	pg/mg
	Liu et al. (2008) ⁴¹	Urine	1.7 ± 0.26	0.041 ± 0.026	.000	pg/mg
	Liu et al. (2010) ⁴²	Urine	0.78 ± 1.26	0.01 ± 0.02	.02	pg/mg
		Urothelium	125.87 ± 21.79	135.60 ± 13.50	.142	pg/mg
	Liu et al. (2011) ⁴³	Serum	Median [IQR]: 0.0 [0–33.6]	0.0728 [0–0.234]	NI	pg/ml
		Urine	Median [IQR]: 0.82 [0.13–1.84]	0.005 [0–0.028]	NI	pg/mg
	Liu et al. (2011) ⁴⁴	Urine	2.13 ± 3.87	0.07 ± 0.21	.000 (ANOVA (control‐dry‐wet)	pg/mg
	Liu et al. (2013) ⁴⁵	Serum	3.66 ± 2.45	2.57 ± 0.88	.045	pg/ml
	Richter et al. (2017)^c ^, ⁴⁷	Urine	6.4 ± 1.5	5.0 ± 1.5	NS difference	pg/mg
	Silva‐Ramos et al. (2013) ⁴⁹	Urine	109.5 ± 29.0	64.0 ± 13.6	.162	pg/mg
NTx	Richter et al. (2017)^c ^, ⁴⁷	Urine	31.4 ± 1.3	15.6 ± 2.1	<.001	nM/mM
P2X(1–7)	Moore et al. (2001) ⁴⁶	PNT	P2X3 and P2X5: 0% and 0%	P2x3 and P2X5 94 and 91%	NI	%
			P2X4, P2X6, and P2X7: 36%, 33%, and 67%	P2X4, P2X6, P2X7: 16%, 18%, and 6%	<.0001 in all
			P2X1 and P2X2: 96% and 99%	P2X1 and P2X2: 97% and 99%	0.32 and 0.16
Parathormone	Ustundag et al. (2019) ⁵⁰	Serum	Median [IQR]: 6.68 [4.0]	6.15 [3.9]	0.715	pmol/L
Polyamines	Li et al. (2013) ⁴⁰	Urothelium	Putrescine: 0.50 ± 0.15	Putrescine: 0.16 ± 0.03	<.05	nmol/mg
			Spermidine: 2.4 ± 0.21	Spermidine: 1.0 ± 0.13	<.01	nmol/mg
			Spermine: 1.9 ± 0.27	Spermine: 0.86 ± 0.26	<.05	nmol/mg
PON	Keske et al. (2019) ³⁴	Serum	Median [IQR]: 144.1 [91.6–249.5]	158.6 [91.1–280.8]	.934	NI
Slo	Meredith et al. (2004) ²¹	Mutated mice	Slo^−/− mice exhibited UUI phenotype compared with controls
	Thorneloe et al. (2005) ²²	Mutated mice	Slo^−/− mice exhibited UUI phenotype compared with controls
Stem cell factor	Kubota et al. (2018) ³⁶	Urine	Median [IQR]: 1.30 [0.56–2.71]	0.26 [0.13–0.43]	<.0001	pg/mg
Substance P	Richter et al. (2017)^c ^, ⁴⁷	Urine	257.5 ± 0.9	271.5 ± 1.1	NS difference	pg/mg
TAC	Keske et al. (2019) ³⁴	Serum	1.8 ± 0.199	2.1 ± 0.216	<.001	NI
Thiol, native	Ustundag et al. (2019) ⁵⁰	Serum	331 ± 64	356 ± 73	.156	µmol/L
Thiol, total	Ustundag et al. (2019) ⁵⁰	Serum	365 ± 65	394 ± 70	.095	µmol/L
TNF‐α	Liu et al. (2013) ⁴⁵	Serum	3.30 ± 2.60	0.91 ± 0.84	.000	pg/ml
	Richter et al. (2017)^c ^, ⁴⁷	Urine	All below assay sensitivity			pg/ml
TOS	Keske et al. (2019) ³⁴	Serum	4.7 ± 1.77	4.1 ± 1.46	.109	NI
Triglyceride	Ustundag et al. (2019) ⁵⁰	Serum	1.84 ± 1.08	1.86 ± 1.12	.927	mmol/L
Tropoelastin	Richter et al. (2017)^c ^, ⁴⁷	Urine	17.1 ± 0.9	9.6 ± 1.2	.001	mg/mg
TRPV1	Birder et al. (2013) ²⁹	HBUC	Statistically significant higher receptor expression in UUI versus controls (shown in figure, exact data not shown)
	Li et al. (2011) ²⁵	Urothelium	0.25 ± 0.005	0.125 ± 0.01	<.05	Mean density ratio
	Liu et al. (2007) ²⁶	Urothelium	Bladder body median [IQR]: 11.4 [6.7–16.1]	14.2 [8.2–20.7]	NS difference	10⁵ Copies/µg
	Liu et al. (2007) ²⁶	Urothelium	Trigonum median [IQR]: 10.9 [8.5–15.7]	4.1 [0.77–26.2]	NS difference	Total RNA
VEGF	Christiaansen et al. (2011) ²⁴	HBUC	23.51 ± 9.88%	24.52 ± 4.68%	NS difference	%
Vinculin	Carey et al. (2000) ³⁰	Detrusor muscle	No apparent differences between the groups
Vitamin D	Ustundag et al. (2019) ⁵⁰	Serum	Median [IQR]: 27.0 [27.5]	33.7 [30.7]	.081	nmol/L

^{^a}

All urinary values are adjusted to urinary creatinine levels.

^{^b}

Data are presented as means ± SD unless otherwise described.

^{^c}

Data log‐transformed before analysis.

Abbreviations: AIP, atherogenic index of plasma; ANOVA, analysis of variance; AOPP, advanced oxidation protein products; ATP, adenosine triphosphate; B1 integrin, β1 integrin; B3‐AR, β‐3 adrenergic receptor; BDNF, brain‐derived neurotrophic factor; CGRP, calcitonin gene‐related peptide; CRP, C‐reactive protein; FRAP, ferric reducing power of plasma; GAG, glycosaminoglycans; GAP‐43, growth association protein 43; GDNF, glial cell line‐derived neurotrophic factor; GMC‐SF, granulocyte‐macrophage colony‐stimulating factor; HB‐EGF, heparin‐binding epidermal growth factor‐like growth factor; HBUC, human bladder urothelium cells; HDL, high‐density lipoprotein; HIF, hypoxia‐inducible factor; IL, interleukin; IMA, ischemia modified albumin; IQR, interquartile ratio; LDL, low‐density lipoprotein; M2/3R, muscarinic 2/3 receptor; MCP‐1, monocyte chemoattractant protein‐1; MMP, matrix metalloproteinase; M‐Ras, muscarinic‐Ras; NA, not applicable; NGF, nerve growth factor; NI, no information; NTx, N‐terminal telopeptide type 1 collagen; PNT, parasympathic nerve tissue; PON, paraoxonase; TAC, total antioxidant capacity; TNF‐α, tumor necrosis factor α; TOS, total oxidant status; TRPV1, transient receptor potential cation channel subfamily V member 1; VEGF, vascular endothelial growth fac.