Association of serotonin receptor 2a haplotypes with obsessive–compulsive disorder and its treatment response in Iranian patients: a genetic and pharmacogenetic study

Figures & data

Table 1 Sociodemographic characteristics of OCD patients (N=293)

	n	%
Sex
Female	204	69.6
Male	89	30.3
Marital status
Single	82	27.9
Married	211	72.0
Level of education
School dropout	87	29.6
Diploma	133	45.3
Undergraduate	59	20.1
Graduate	12	4.0
Missing	2	0.6
Occupation
Unemployed	175	59.7
Employed	117	39.9
Missing	1	0.3
Age of onset
Early	82	27.9
Late	210	71.6
Missing	1	0.3
Familial history of psychiatric disorders
Positive history	233	79.5
Negative history	60	20.4
	Mean	SD
Age (years)
Age at assessment	35.03	10.34
Age of symptoms onset	24.73	10.77
Y-BOCS current severity
Obsession	10.89	4.65
Compulsion	9.40	5.66
Total score	20	8.63

Abbreviations: OCD, obsessive–compulsive disorder; Y-BOCS, Yale–Brown Obses sive Compulsive scale.

Figure 1 Flow diagram of the study progress.

Abbreviation: Y-BOCS, Yale–Brown Obsessive Compulsive Scale.

Table 2 Genotype distribution of the HTR2A polymorphisms in OCD patients and controls under different genetic models considering sex

rs6311	Controls		Patients		P-value	OR	Lower–upper
	n	%	n	%
Co-dominance
Female
GG	27	23.4	61	30.3	0.310
GA	64	55.6	95	47.3
AA	24	22	45	23.4
Male
GG	24	19.5	26	30.0	0.065
GA	68	55.2	34	39.6
AA	31	25.2	26	30.3
Total
GG	51	21.4	87	30.3	0.031
GA	132	55.4	129	44.9
AA	55	23.3	71	24.7
Dominance
Female
GG+GA	91	79.1	156	77.6	0.753	1.094	0.626–1.912
AA	24	20.8	45	22.3
Male
GG+GA	92	74.7	60	69.7	0.422	1.028	0.696–2.377
AA	31	25.2	26	30.23
Total
GG+GA	183	76.8	216	75.2	0.662	1.094	0.731–1.637
AA	55	23.1	71	24.7
Recessive
Female
GG	27	23.4	63	31.3	0.126	0.672	0.398–1.135
GA+AA	88	76.5	138	68.6
Male
GG	24	19.5	26	30.2	0.074	0.559	0.295–1.062
GA+AA	99	80.4	60	69.7
Total
GG	51	21.4	89	31.0	0.013	0.607	0.408–0.903
GA+AA	187	78.5	198	68.9
rs6313	Controls		Patients		P-value	OR	Lower–upper
	n	%	n	%
Co-dominance
Female
CC	29	25	63	31.0	0.465
CT	61	52.5	94	46.3
TT	26	22.4	46	22.6
Male
CC	34	27.4	27	30.3	0.204
CT	64	51.6	36	40.4
TT	26	20.9	26	29.2
Total
CC	63	26.2	90	30.8	0.180
CT	125	52.0	130	44.5
TT	52	21.6	72	24.6
Dominance
Female
CC+CT	90	77.3	157	77.3	0.992	1.003	0.581–1.733
TT	26	22.6	46	22.6
Male
CC+CT	98	79.2	63	70.7	0.157	1.571	0.838–2.947
TT	26	20.8	26	29.2
Total
CC+CT	188	78.3	220	75.3	0.417	1.183	0.788–1.776
TT	52	21.6	72	24.6
Recessive
Female
CC	29	25.2	63	31.0	0.272	0.749	0.448–1.255
CT+TT	87	74.7	140	68.9
Male
CC	34	27.2	27	30.3	0.616	0.858	0.471–1.563
CT+TT	90	72.8	62	69.6
Total
CC	63	26.2	90	30.8	0.246	0.799	0.546–1.168
CT+TT	177	73.7	202	69.6

Note: Statistical significance considered as P-value <0.008.

Abbreviations: OCD, obsessive–compulsive disorder; OR, odds ratio.

Table 3 Genotype distribution of the HTR2A polymorphisms in familial form of OCD under different genetic models considering sex

rs6311	Family history				P-value	OR	Lower–upper
	Negative		Positive
	n	%	n	%
Co-dominance
Female
GG	23	46	39	26	0.040
GA	17	34	76	50.6
AA	10	20	35	23.3
Male
GG	1	12.5	24	31.1	0.375
GA	3	37.5	31	40.2
AA	4	50	22	28.5
Total
GG	24	40.3	63	27.7	0.144
GA	20	35.0	107	47.1
AA	14	24.5	57	25.1
Dominance
Female
GG+CT	40	80	115	76.6	0.391	1.217	0.553–2.681
AA	10	20	35	23.3
Male
GG+CT	4	50	55	76.6	0.195	0.400	0.092–1.742
AA	4	50	22	71.4
Total
GG+CT	44	75.8	170	74.8	0.514	1.054	0.538–2.064
AA	14	24.1	57	25.1
Recessive
Female
GG	22	44	39	71.4	0.014	2.236	1.148–4.357
GA+AA	28	56	111	28.5
Male
GG	1	12.5	24	31.1	0.254	0.315	0.037–2.708
GA+AA	7	87.5	53	68.8
Total
GG	23	39.6	63	27.7	0.056	1.711	0.938–3.120
GA+AA	35	60.3	164	72.2

Note:

* P-value <0.008.

Abbreviations: OCD, obsessive–compulsive disorder; OR, odds ratio.

Table 4 Haplotype association analysis of HTR2A polymorphisms rs6311 and rs6313 with OCD

Haplotype	rs6311	rs6313	Controls		Patients		P-value
			n	%	n	%
H1	G	C	467	40.9	295	31.2	0.047*
H2	G	T	135	11.8	167	17.6	0.117
H3	A	C	141	12.3	197	20.8	0.029*
H4	A	T	397	34.8	285	30.1	0.336

Note:

* P-value <0.05.

Abbreviation: OCD, obsessive–compulsive disorder.

Table 5 Genetic association analyses of the HTR2A polymorphisms with OCD treatment response under different genetic models considering sex

rs6311	Responders		Non-responders		Refractory		P-value
	n	%	n	%	n	%
Co-dominance
Female
GG	11	21.5	5	25	3	20	0.281
GA	29	56.8	6	30	8	53.3
AA	11	21.5	9	45	4	26.6
Male
GG	7	25	2	22.2	1	12.5	0.856
GA	11	39.8	5	55.5	4	50
AA	10	35.7	2	22.2	3	37.5
Total
GG	18	22.78	7	24.1	4	17.3	0.730
GA	40	50.6	11	37.9	12	52.1
AA	21	26.5	11	37.9	7	30.4
Dominance
Female
GG+GA	40	50.6	11	55	11	73.3	0.140
AA	11	13.9	9	45	4	26.6
Male
GG+GA	18	64.2	7	77.7	5	62.5	0.728
AA	10	35.7	2	22.2	3	37.5
Total
GG+GA	58	73.4	18	62.0	16	69.5	0.519
AA	21	26.5	11	37.9	7	30.4
Recessive
Female
GG	11	21.5	5	55	3	20	0.930
GA+AA	40	78.4	15	45	12	80
Male
GG	7	25	2	77.7	1	12.5	0.755
GA+AA	21	75	7	22.2	7	87.5
Total
GG	18	22.7	7	24.1	4	17.3	0.824
GA+AA	61	77.2	22	75.8	19	82.6
rs6313	Responders		Non-responders		Refractory		P-value
	n	%	n	%	n	%
Co-dominance
Female
CC	13	25	6	30	3	20	0.111
CT	29	55.7	5	25	9	60
TT	10	19.2	9	45	3	20
Male
CC	7	25	2	22.2	1	12.5	0.904
CT	12	42.8	5	55.5	4	50
TT	10	32.1	2	22.2	3	37.5
Total
CC	20	25	8	27.5	4	17.3	0.436
CT	41	51.2	10	34.4	13	56.5
TT	19	23.7	11	37.9	6	26.0
Dominance
Female
CC+CT	42	80.7	11	55	12	80	0.069
TT	10	19.2	9	45	3	20
Male
CC+CT	19	67.8	7	77.7	5	62.5	0.780
TT	9	32.1	2	22.2	3	37.5
Total
CC+CT	61	76.2	18	62.0	17	73.9	0.337
TT	19	23.7	11	37.9	6	26.0
Recessive
Female
CC	13	25	6	30	3	20	0.795
CT+TT	39	75	14	70	12	80
Male
CC	7	25	2	22.2	1	12.5	0.755
CT+TT	21	75	7	77.7	7	87.5
Total
CC	20	25	8	27.5	4	17.3	0.674
CT+TT	60	75	21	72.4	19	82.6

Note: Statistical significance considered as P-value <0.008.

Abbreviation: OCD, obsessive–compulsive disorder.

Table 6 Haplotype association analysis of HTR2A polymorphisms rs6311 and rs6313 with OCD treatment response

Haplotype	rs6311	rs6313	Responders		Non-responders		Refractory		P-value
			n	%	n	%	n	%
H1	G	C	112	35.6	39	37.1	25	27.1	0.072
H2	G	T	38	12.1	11	10.4	15	16.3	0.185
H3	A	C	46	14.6	0	0	17	18.4	0.0001*
H4	A	T	118	37.5	55	52.3	35	38.0	0.004*

Note:

* P-value <0.05.

Abbreviation: OCD, obsessive–compulsive disorder.