IgE-Mediated Systemic Anaphylaxis And Its Association With Gene Polymorphisms Of ACE, Angiotensinogen And Chymase

Figures & data

Figure 1 Terr’s classification of anaphylaxis grades 1–4.

Note: Data from Terr.¹

Figure 2 Tri-allelic ensemble of the 27 genes combinations of AGT, CMA1 and ACE for healthy controls (HC) and anaphylaxis.

Note: *Genes in the analysis.

Table 7 Ensemble Of 6 Common Gene Combinations

Tri-Allelic Ensemble	HC (No. Of Cases)	Anaphylaxis (No. Of Cases)	AACVS (No. Of Cases)
II or ID MM AG	11	29	26
DD MT AG or GG	29	7	6
DD MM AG	8	6	4
ID MT AG	10	16	8
Total no. (% of total in group)	47 (40%)	58 (48%)	44 (46%)
Chi square HC versus anaphylaxis* andAACVS*	–	Anaphylaxis P=0.0001*	AACVS P=0.0001*

Note: *Chi-square analysis with significance p<0.025.

Abbreviation: AACVS, airway angioedema ± cardiovascular collapse.

Table 1 Demographics Of Subjects

Subject Groups	Mean Age ±SD (Age Range)	Serum ACE±SD Levels U/L	Ethnic Groups	Allergen Sensitivity And (Number Of Subjects)
Healthy controls N=119 (73% female)	53±11.1 (25–71)	48.9±25	95% Caucasian 5% Asian	None
Atopic controls N=52 (77% female)	47±13.7 (18–77)	47.9±25	87% Caucasian Asian 10% Chinese 3%	Fish (3) Dairy (3) Fruit/nut (13) Airborne (33)
Anaphylaxis group (venom, food & drug) N=122 (65% female)	45±14.0 (16–71)	33.8±21	93% Caucasian Asian 6% African-American=1%	Wasp (35) Bee (9) Nut/fruit (36) Latex/others (13) Drugs (6) Exercise (4) Cereals (5) Fish (14)
Cause of anaphylaxis and no. of subjects	Venom n=44		Foods/drugs/latex N=78
Symptom onset  <10mins  10–30mins  >30mins	65% 8% 27%		66% 46% 30%
Total no. of anaphylaxis (mean no. per subject)	94 stings (2.1 each)		170 reactions (2.6 each)
AACVS reaction for venom/foods	84% (n=37 subjects)		74% (n=58 subjects)
Terr’s classification of anaphylaxis	Venom 44 subjects		Food/drug/latex 78 subjects	Total of subjects in each grade
Grade 1	2		8	10
Grade 2	16		39	55
Grade 3	24		28	52
Grade 4	2		3	5

Abbreviation: AACVS, angioedema and cardiovascular collapse.

Table 2 Angiotensinogen Genes For The Groups And Terr’s Classification

AGT Genotype (% Of Cases)	MM	MT	TT	Healthy Controls*	Atopics*	Anaphylaxis*	CRA*
Healthy controls (HC) N=119	42 (35%)	63 (53%)	14 (12%)
Atopic controls N=52	20 (38%)	24 (46%)	8 (16%)	P=0.671
Anaphylaxis N=122	56 (46%)	43 (35%)	23 (19%)	P=0.019	P=0.399
CRA^+ anaphylaxis only N=27	11 (41%)	11 (41%)	5 (18%)	P=0.449	P=0.883	P=0.89
AACVS^+ anaphylaxis N=95	45 (48%)	32 (33%)	18 (19%)	P=0.017	P=0.330	P=0.98	P=0.778
Significance	The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example healthy control versus anaphylaxis p =0.019.*Chi square with 2df with significance at < 0.005. CRA^+= cutaneous & respiratory anaphylaxis. AACVS^+= airway angioedema ± cardiovascular collapse
Terr’s Traditional Grades Of Anaphylaxis	MM	MT	TT	Grade 1 P value^#	Grade 2 P value^#	Grade 3* P value#
Grade 1 N=10	0	9	1
Grade 2 N=55	26	16	13	P=0.0011
Grade 3 N=52	27	16	9	P=0.0017	P=0.718
Grade 4 N=5	3	2	0	P=0.220	P=0.468	P=0.593
Statistical significance	*Chi square with 2df with ^#p-value significant <0.008.The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example grade 1 versus grade 4 Terr p =0.220

Table 3 Chymase CMA1-1903 Genotype Frequency For The Groups

Chymase Genotype (% Of Cases)	AA	AG	GG	Healthy* Controls	Atopics*	Cutaneous* & RS
Healthy controls (HC)n=119	23 (19%)	65 (55%)	31 (26%)
Atopic controlsn=52	7 (14%)	32 (61%)	13 (25%)	P=0.597
Anaphylaxis n=122	19 (16%)	66 (54%)	37 (30%)	P=0.648	P=0.661
CRA n=27	1 (3%)	15 (56%)	11 (41%)	P=0.072	P=0.1991
AACVS n=95	18 (19%)	51 (54%)	26 (27%)	P=0.976	P=0.596	P=0.111

Notes: *Chi-square with 2df with significance at p<0.006. The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example healthy controls versus CRA p =0.072.

Abbreviations: CRA, cutaneous & respiratory anaphylaxis; AACVS, airway angioedema ± cardiovascular collapse.

Table 4 Chymase CMA-1 A1903G And AGT M235T Bi-Allelic Pairing For The Groups

Shared Genotype (% Of Cases)	MM/AA	MM/AG	MM/GG	MT/AA	MT/AG	MT/GG	TT/AA	TT/AG	TT/GG	HC*	Atopics*	Anaphylaxis*
Healthy controls (HC)n=119	7 (6%)	20 (17%)	16 (13.5%)	10 (8%)	37 (31%)	16 (13.5%)	6 (5%)	6 (5%)	1 (1%)
Atopic controlsn=52	2 (4%)	12 (23%)	6 (11%)	2 (4%)	16 (31%)	5 (9.5%)	2 (4%)	5 (9.5%)	2 (4%)	P=0.67
Anaphylaxisn=122	9 (7%)	38 (31%)	11 (9%)	7 (6%)	21 (17%)	15 (13%)	3 (2%)	7 (6%)	11 (9%)	P=0.005	P=0.47
CRA n=27	0	6 (22%)	5 (19%)	1 (4%)	6 (22%)	3 (11%)	0	2 (7%)	4 (15%)	P=0.063
AACVS n=95	9 (10%)	32 (34%)	6 (6%)	6 (6%)	15 (16%)	12 (13%)	3 (3%)	5 (5%)	7 (7%)	P=0.005		P=0.99

Notes: The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example HC versus anaphylaxis p =0.005. *Chi square with 2df with significance at p< 0.008.

Abbreviations: CRA, cutaneous & respiratory anaphylaxis; AACVS, airway angioedema ± cardiovascular collapse.

Table 5 AGT M235T And ACE I/D Gene Bi-Allelic Pairing For The Groups

Shared Genotype (% Of Cases)	MM/II	MM/ID	MM/DD	MT/II	MT/ID	MT/DD	TT/II	TT/ID	TT/DD	HC*	Atopic*	Anaphylaxis*
Healthy controls (HC)n=119	7 (5%)	20 (18%)	16 (14%)	12 (10%)	19 (16%)	32 (27%)	4 (3%)	5 (4%)	4 (3%)
Atopic controlsn=52	3 (6%)	12 (23%)	5 (10%)	3 (6%)	9 (17%)	12 (23%)	2 (4%)	6 (11%)	0	P=0.6
Anaphylaxisn=122	18 (15%)	29 (24%)	9 (7%)	7 (6%)	26 (21%)	10 (8%)	8 (7%)	10 (8%)	5 (4%)	P=0.0013*	P=0.159
CRA n=27	3 (11%)	7 (26%)	2 (7.5%)	0	7 (26%)	3 (11%)	0	3 (11%)	2 (7%)	P=0.089	P=0.133	P=0.83
AACVS n=95	15 (16%)	22 (24%)	7 (7%)	7 (7%)	19 (20%)	7 (7%)	8 (9%)	7 (7%)	3 (3%)	P=0.0030*	P=0.416	P=0.999

Notes: The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example HC versus anaphylaxis p =0.0013. *Chi-square with 2df with significance at p< 0.005.

Abbreviations: CRA, cutaneous & respiratory anaphylaxis; AACVS, airway angioedema ± cardiovascular collapse.

Table 6 Bi-Allelic Pairing Of Chymase CMA-1 A1903G And ACE I/D Gene Combinations For The Different Groups

Shared Genotype (% Of Cases)	AA/II	AA/ID	AA/DD	AG/II	AG/ID	AG/DD	GG/II	GG/ID	GG/DD	HC*	Atopic*	Anaphylaxis*
Healthy controls (HC)n=119	4 (3%)	12 (10%)	7 (6%)	12 (10%)	21 (18%)	30 (25%)	6 (5%)	13 (11%)	14 (12%)
Atopic controlsn=52	0	4 (8%)	3 (6%)	8 (15%)	16 (31%)	8 (15%)	0	7 (14%)	6 (11%)	P=0.03
Anaphylaxis n=122	8 (6.5%)	8 (6.5%)	3 (2%)	15 (13%)	40 (33%)	11 (9%)	10 (8%)	17 (14%)	10 (8%)	P=0.007*	P=0.14
CRA n=27	0	0	1 (3%)	0	12 (44%)	3 (12%)	2 (7%)	6 (22%)	3 (12%)	P=0.022		P=0.26
AACVS n=95	8 (8%)	8 (8%)	2 (2.5%)	15 (16%)	28 (30%)	8 (8%)	8 (8%)	11 (12%)	7 (7.5%)	P=0.013		P=0.99

Notes: The p values for the groups and subgroups are represented as a chequer board with significant values in bold for example HC versus anaphylaxis p =0.007. *Chi-square with 2df with significance at p< 0.007.

Abbreviations: CRA, cutaneous & respiratory anaphylaxis; AACVS, airway angioedema ± cardiovascular collapse.

Figure 3 Diagram of the renin-angiotensin-aldosterone system.

Terr AI. Anaphylaxis. Clin Rev Allergy. 1985;3:3–23.3884127

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