ABCB1 and ABCC1 single-nucleotide polymorphisms in patients treated with clozapine

Figures & data

Table 1 Descriptive statistics and distribution of patient data

	N statistic	Minimum statistic	Maximum statistic	Mean statistic	SD statistic	Skewness		Kurtosis
						Statistic	SE	Statistic	SE
Age	174	17.53	67.44	42.40	10.98	0.35	0.18	−0.44	0.37
BMI at CZ commencement	106	17.68	73.90	30.09	8.29	2.15	0.24	7.63	0.47
BMI after 3 months	114	18.68	63.83	30.55	7.68	1.61	0.23	4.01	0.45
BMI after 12 months	119	19.30	71.35	31.47	8.33	1.81	0.22	5.34	0.44
Delta BMI after 3 months	99	−10.08	3.82	0.31	1.76	−2.18	0.24	11.51	0.48
Delta BMI after 12 months	101	−12.09	11.03	0.87	3.86	−0.45	0.24	2.02	0.48
Systolic BP (mmHg)	164	91.80	296.83	126.18	18.29	5.11	0.19	46.19	0.38
Diastolic BP (mmHg)	164	41.50	108.00	85.11	9.30	−0.51	0.19	2.52	0.38
Clozapine dose (mg)	146	50.00	825.00	356.84	169.35	0.55	0.20	−0.53	0.40
Clozapine level (ng/mL)	157	55.00	2087.50	533.41	345.97	1.46	0.19	3.09	0.39
Norclozapine level (ng/mL)	156	46.25	817.50	271.30	150.82	0.89	0.19	0.49	0.39
Ratio CZ/NCZ	158	0.82	3.58	1.96	0.54	0.68	0.19	0.60	0.38
White cell count (×10^9/L)	140	3.60	36.77	7.84	3.14	5.74	0.21	51.25	0.41
Fasting glucose (mmol/L)	164	4.07	19.70	6.40	2.60	2.98	0.19	9.67	0.38
Random glucose (mmol/L)	33	3.90	62.00	8.25	10.29	4.86	0.41	25.01	0.80
HbAlc (mmol/mol)	46	28.00	111.00	46.79	18.04	1.78	0.35	3.18	0.69
Total cholesterol (mmol/L)	169	2.77	8.50	5.17	1.04	0.59	0.19	0.37	0.37
LDL cholesterol (mmol/L)	164	1.10	6.02	3.02	0.89	0.69	0.19	1.06	0.38
HDL cholesterol (mmol/L)	167	0.60	2.07	1.17	0.29	0.53	0.19	0.05	0.37
Triglycerides (mmol/L)	111	0.60	11.50	2.47	1.72	2.52	0.23	8.10	0.46
Prolactin (mIU/L)	4	77.00	253.00	129.25	83.60	1.85	1.01	3.44	2.62
eGFR (mL/min/1.73 m^2)	7	89.00	90.00	89.86	0.38	−2.65	0.79	7.00	1.59

Abbreviations: BMI, body mass index; CZ, clozapine; BP, blood pressure; LDL, low-density lipoprotein; HDL, high-density lipoprotein; NCZ, norclozapine; eGFR, estimated glomerular filtration rate; SD, standard deviation; SE, standard error.

Table 2 ABCB1 and ABCC1 genotypes and BMI at clozapine commencement

	N	Mean	Standard deviation	95% Confidence interval for mean		t-test two-tailed p*	After normalization to age (regression analysis*)
							Female			Male
				Lower	Upper		R^2	beta	p	R^2	beta	p
BMI at clozapine commencement
ABCB1
Noncarriers	25	31.93	10.81	27.47	36.40
Heterozygotes	30	28.21	5.10	26.30	30.11
Homozygotes	13	28.71	7.29	24.30	33.12	0.095	0.187	0.168	0.404	0.211	−0.380	0.009
ABCC1
Noncarriers	30	31.17	10.03	27.42	34.91
Heterozygotes	38	28.92	6.00	26.94	30.89
Homozygotes	9	26.89	3.75	24.01	29.78	0.060	0.138	0.101	0.594	0.134	−0.279	0.054

Note:

* Between presence and absence of polymorphisms.

Abbreviation: BMI, body mass index.

Figure 1 Changes in BMI after 3 months of clozapine commencement in carriers versus noncarriers of polymorphisms.

Abbreviation: BMI, body mass index.

Figure 2 Changes in BMI after 12 months of clozapine commencement in carriers versus noncarriers of polymorphisms.

Abbreviation: BMI, body mass index.

Table 3 Changes in BMI (ΔBMI) after 3 and 12 months from clozapine commencement and transporter polymorphisms

Changes in BMI after clozapine commencement	SNP	t-test (two-tailed)				After normalization to age (regression analysis)
		N	Mean kg/m^2	SD	Sig	Female			Male
						r^2	beta	Sig	r^2	beta	Sig
ABCB1
ΔBMI after 3 months on clozapine	Noncarriers	25	−0.095	2.511
	Carriers	40	0.575	1.321	0.227	0.226	0.234	0.244	0.149	−0.316	0.026
ΔBMI after 12 months on clozapine	Noncarriers	25	0.264	4.063
	Carriers	42	2.252	4.953	0.080	0.148	0.209	0.323	0.067	−0.240	0.086
ABCC1
ΔBMI after 3 months on clozapine	Noncarriers	29	0.155	2.384
	Carriers	45	0.481	1.457	0.513	0.149	0.550	0.587	0.091	−0.220	0.112
ΔBMI after 12 months on clozapine	Noncarriers	28	0.702	3.858
	Carriers	48	1.920	4.905	0.235	0.109	0.123	0.524	0.080	−0.259	0.022

Abbreviations: BMI, body mass index; SNP, single-nucleotide polymorphism; SD, standard deviation; Sig, significance.

Table 4 Blood pressure and transporter polymorphisms

Blood pressure (mmHg)	SNPs	ABCB1					ABCC1
		N	Mean	SD	F	Sig*	N	Mean	SD	F	Sig*
Systolic	Noncarriers	36	124.63	12.36	0.671	0.513	45	129.83	28.61	1.083	0.342
	Heterozygotes	46	126.32	28.47			62	124.11	13.52
	Homozygotes	23	131.07	13.03			14	128.17	9.17
Diastolic	Noncarriers	36	84.86	11.12	6.713	0.002	45	87.20	8.98	3.042	0.051
	Heterozygotes	46	82.24	8.78			62	82.86	10.82
	Homozygotes	23	91.25	8.74			14	87.30	6.11

Note:

* Between groups

Abbreviations: SNP, single-nucleotide polymorphism; SD, standard deviation; Sig, significance.

Table 5 Gender differences in blood pressure and genotype

Genotype	Gender	Systolic (mmHg)			Diastolic (mmHg)
		Mean	N	SD	Mean	N	SD
ABCB1
Noncarriers	Female	120.75	13	12.20	82.72	13	8.99
	Male	126.82	23	12.18	86.08	23	12.19
Heterozygotes	Female	127.06	17	45.08	80.02	17	9.77
	Male	125.89	29	11.85	83.55	29	8.04
Homozygotes	Female	122.22	5	7.40	86.77	5	9.06
	Male	133.53	18	13.32	92.50	18	8.49
ABCC1
Noncarrier	Female	131.16	14	48.63	81.11	14	6.90
	Male	129.23	31	13.20	89.96	31	8.53
Heterozygotes	Female	117.91	21	11.46	80.81	21	10.05
	Male	127.29	41	13.51	83.91	41	11.17
Homozygotes	Female	127.46	4	9.75	87.90	4	6.26
	Male	128.46	10	9.46	87.07	10	6.38

Abbreviation: SD, standard deviation.