TP53 codon 72 Arg/Arg polymorphism is associated with a higher risk for inflammatory bowel disease development

Table 1 Summary of biological and biochemical differences between ⁷²Arg and ⁷²Pro TP53 isoforms

Property	72Arg vs72Pro TP53
Electrophoretic mobility	72Arg migrates slightly faster on SDS[16,19,20]
Subcellular localization	72Arg is cytoplasmic/mitochondrial possibly through interaction with CD2AP/Cin85 adaptor protein family[21] or with mitochondrial (mt) polymerase gamma, which may also promote mtDNA repair[22,23] 72Pro is predominantly nuclear[21,24]
Apoptosis induction	72Arg is a stronger apoptosis inducer[24], with faster kinetics of cell death[16] possibly through more efficient inhibition of 72Pro by iASPP[25] or preferential localization of 72Arg to mitochondria and induction of apoptosis through a transcriptionally independent pathway[24]
Suppression of transformed cell growth	72Arg is two times more active in suppressing colony formation[16]
Susceptibility to HPV E6 degradation	72Arg is more susceptible to degradation[26,27]
Transcription activation	72Arg associates and inactivates p73 more efficiently[20], thus inhibiting apoptosis72Pro is a stronger inducer of transcription and it has more affinity to TAFII32 and TAFII70[16]
Leukemia inhibitory factor transactivation	72Arg is more active towards this function[28,29], which may be advantageous in cold climates due to increased fertility[18]

Table 2 Allele frequencies of TP53⁷²Arg/Pro polymorphism in cases and controls n (%)

Patients/Controls	Allele		P value1
	Arg	Pro
Cases (n = 642):	974 (75.9)	310 (24.1)	< 0.0001
UC Adult (n = 151)	222 (73.5)	80 (26.5)	0.0029
CD Adult (n = 138)	210 (76.1)	66 (23.9)	0.0005
UC Pediatric (n = 78)	118 (75.6)	38 (24.4)	0.0028
CD Pediatric (n = 94)	145 (77.1)	43 (22.9)	0.0006
PSC (n = 42)	67 (79.8)	17 (20.2)	0.0016
PSC + UC (n = 139)	212 (76.3)	66 (23.7)	0.0004
Controls (n = 62)	73 (58.9)	51 (41.1)

¹P value calculated by χ² test for comparison of patient groups with controls.

Table 3 Genotype frequencies of TP53 polymorphism in cases and controls

Patients/controls	Genotype, % (n)			OR1	95%CI	P value
	Arg/Arg	Arg/Pro	Pro/Pro
Cases (n = 642):	56.9 (365)	38.0 (244)	5.1 (33)	2.77	1.59-4.82	0.0001
UC adult (n = 151)	54.3 (82)	38.4 (58)	7.3 (11)	2.50	1.34-4.65	0.0102
CD adult (n = 138)	55.8 (77)	40.6 (56)	3.6 (5)	2.65	1.41-4.98	0.0011
UC pediatric (n = 78)	55.1 (43)	41.0 (32)	3.8 (3)	2.58	1.29-5.17	0.0078
CD pediatric (n = 94)	59.6 (56)	35.1 (33)	5.3 (5)	3.09	1.58-6.07	0.0023
PSC (n = 42)	64.3 (27)	31.0 (13)	4.8 (2)	3.78	1.66-8.63	0.0046
PSC + UC (n = 139)	57.6 (80)	37.4 (52)	5.0 (7)	2.85	1.52-5.35	0.0016
Controls (n = 62)	32.3 (20)	53.2 (33)	14.5 (9)

¹OR is calculated for Arg/Arg vs Arg/Arg + Pro/Pro. CD: Crohn’s disease; UC: Ulcerative colitis; PSC: Primary sclerosing cholangitis.