Association of Cholinergic Muscarinic M4 Receptor Gene Polymorphism with Schizophrenia

Figures & data

Figure 1 Genomic location of CHRM4 gene. Genomic location of the CHRM4 gene (chr15:46,200,000–47,300,000). Yellow lines highlight the location of two investigated variants in CHRM4 gene, rs2067482 and rs72910092. PACSIN3 gene is marked by green rectangle.

Table 1 Characteristics of Schizophrenia and Control Groups

Parameter	Schizophrenia Group	Control Group
Sex, n (%)	Male – 223 (49.7%) Female – 226 (50.3%)	Male – 62 (46.3%) Female – 72 (53.7%)
Age, years	41.72 ± 13.315	38.53 ± 12.154
Age of onset, years	26.21 ± 8.975	–
Duration of disease, years	15.60 ± 11.418	–

Table 2 Frequency of CHRM4 Genotypes and Alleles in Patients with Schizophrenia and Healthy Controls

SNP	Genotypes/Alleles	Schizophrenia Patients (1)	Healthy Controls (2)	HWE (χ^2; p)	OR		χ^2	p
					Value	95% CI
rs2067482	CC	303 (68.2%)	109 (81.3%)	χ1^2 = 0.01 p1 = 0.91	0.49	0.31–0.80	9.167	0.010^a
	CT	128 (28.8%)	2 (17.9%)		1.86	1.14–3.02
	TT	13 (2.9%)	1 (0.7%)	χ2^2 = 0.07 p2 = 0.80	4.01	0.52–30.95
	C	0.827	0.903		0.51	0.33–0.80	9.14	0.003^a
	T	0.173	0.097		1.95	1.26–3.03
rs72910092	CC	413 (92.6%)	127 (94.8%)	χ1^2 = 0.66 p1 = 0.42	0.69	0.30–1.60	0.759	0.384
	CT	33 (7.4%)	7 (5.2%)		1.45	0.63–3.36
	TT	0 (0.0%)	0 (0.0%)	χ2^2 = 0.10 p2 = 0.76	–	–
	C	0.963	0.974		0.70	0.31–1.60	0.73	0.39
	T	0.037	0.026		1.43	0.63–3.28

Note: ^ap-Values stay significant after Bonferroni correction for multiple testing.

Table 3 Frequency of CHRM4 Genotypes and Alleles in Schizophrenia Patients with Different Types of Course of the Disease (Continuous vs Episodic)

SNP	Genotypes/Alleles	Patients with Continuous Type, %	Patients with Episodic Type, %	OR		χ^2	p
				Value	95% CI
rs2067482	CC	144 (69.6%)	66 (68.8%)	1.04	0.62–1.75	0.240	0.988
	CT	59 (28.5%)	28 (29.2%)	0.97	0.57–1.65
	TT	4 (1.9%)	2 (2.1%)	0.93	0.17–5.15
	C	0.838	0.833	1.04	0.65–1.64	0.022	0.881
	T	0.162	0.167	0.97	0.61–1.53
rs72910092	CC	196 (94.2%)	89 (90.8%)	1.65	0.67–4.06	1.215	0.270
	CT	12 (5.8%)	9 (9.2%)	0.61	0.25–1.49
	TT	0 (0.0%)	0 (0.0%)	–	–
	C	0.971	0.954	1.62	0.67–3.91	1.171	0.279
	T	0.029	0.046	0.62	0.26–1.49

Table 4 Frequency of CHRM4 Genotypes and Alleles in Schizophrenia Patients with Different Leading Symptoms (Positive vs Negative)

SNP	Genotypes/Alleles	Patients with Positive Symptoms	Patients with Negative Symptoms	OR		χ^2	p
				Value	95% CI
rs2067482	CC	69 (61.6%)	198 (69.2%)	0.71	0.45–1.13	7.267	0.026^a
	CT	43 (38.4%)	79 (27.6%)	1.63	1.03–2.59
	TT	0 (0.0%)	9 (3.1%)	0.13	0.01–2.25
	C	0.808	0.830	0.86	0.58–1.28	0.556	0.455
	T	0.192	0.170	1.16	0.78–1.73
rs72910092	CC	107 (94.7%)	265 (93.3%)	1.28	0.50–3.29	0.261	0.609
	CT	6 (5.3%)	19 (6.7%)	0.78	0.30–2.01
	TT	0 (0.0%)	0 (0.0%)	–	–
	C	0.974	0.967	1.27	0.50–3.22	0.346	0.557
	T	0.026	0.033	0.76	0.30–1.92

Note: ^ap-Value denotes statistical significance at the p < 0.05 level.

Table 5 CHRM4 Genotype Distribution in Schizophrenia Patients with and without Tardive Dyskinesia

SNP	Genotypes/Alleles	With TD	Without TD	OR		χ^2	p
				Value	95% CI
rs2067482	CC	79 (66.4%)	224 (68.9%)	0.89	0.57–1.39	1.489	0.475
	CT	38 (31.9%)	90 (27.7%)	1.22	0.78–1.93
	TT	2 (1.7%)	11 (3.4%)	0.49	0.11–2.23
	C	0.824	0.828	0.97	0.66–1.44	0.02	0.88
	T	0.176	0.172	1.03	0.70–1.52
rs72910092	CC	113 (94.2%)	300 (92.0%)	1.40	0.59–3.31	0.587	0.443
	CT	7 (5.8%)	26 (8.0%)	0.71	0.30–1.69
	TT	0 (0.0%)	0 (0.0%)	–	–
	C	0.971	0.960	1.38	0.59–3.23	0.56	0.45
	T	0.029	0.040	0.72	0.31–1.69

Table 6 CHRM4 Genotype Distribution in Schizophrenia Patients with Tardive Dyskinesia and Healthy Persons

SNP	Genotypes/Alleles	Schizophrenia Patients with TD	Healthy Persons	OR		χ^2	p
				Value	95% CI
rs2067482	CC	79 (66.4%)	109 (81.3%)	0.45	0.25–0.81	7.42	0.02^a
	CT	38 (31.9%)	24 (17.9%)	2.15	1.20–3.86
	TT	2 (1.7%)	1 (0.7%)	2.27	0.20–25.40
	C	0.824	0.903	0.50	0.30–0.85	6.84	0.009^b
	T	0.176	0.097	1.99	1.18–3.37
rs72910092	CC	113 (94.2%)	127 (94.8%)	0.89	0.30–2.61	0.05	0.98
	CT	7 (5.8%)	7 (5.2%)	1.12	0.38–3.30
	TT	0 (0.0%)	0 (0.0%)	–	–
	C	0.971	0.974	0.89	0.31–2.58	0.04	0.83
	T	0.029	0.026	1.12	0.39–3.24

Notes: ^ap-Value denotes statistical significance at the p < 0.05 level. ^bp-Value stays significant after Bonferroni correction for multiple testing.