Association of genetic variants with level of asthma control in the Arab population

Figures & data

Table 1 Candidate genes and their associated SNPs

Gene	SNP_ID	Major/minor	Chromosome #	SNP location	SNP type
ADRB2	rs1042713	G/A	5	Exon 1	Gly16Arg
	rs1042714	C/G	5	Exon 1	Gln27Glu
ADH5	rs1154400	T/C	4	Promoter	Synonymous
ARG1	rs2781659	A/G	6	Promoter	Synonymous
CRHR1	rs1876828	G/A	17	Intron 14	Synonymous
	rs242939	A/G	17	Intron 4	Synonymous
	rs242941	G/T	17	Intron 3	Synonymous
STIP1	rs2236647	T/C	11	Intron 5	Synonymous

Abbreviation: SNP, single-nucleotide polymorphism.

Table 2 Demographic and clinical data of the participants

Characteristicsa	Controlled asthma (n=74)	Uncontrolled asthma (n=171)	P-value
Age at evaluation (years)b	28.73±16.69	30.91±16.34	0.655
Gender			0.581
Male	17 (23)	45 (26.3)
Female	57 (77)	126 (73.7)
Smoking			1.00
Never	71 (95.9)	164 (95.9)
Ex-smoker	3 (4.1)	7 (4.1)
Level of education			0.568
Basic education	43 (58.1)	106 (62)
University degree	31 (41.9)	65 (38)
Personal history of hay fever/eczema	24 (32.4)	56 (32.7)	0.961
Family history of asthma	31 (41.9)	67 (39.2)	0.691
Body mass indexb	29.36±5.3	29.48±6.75	0.190
Comorbid disease	24 (32.4)	65 (38)	0.404
Unscheduled medical intervention	33 (44.6)	126 (73.7)	<0.001
Asthma severity, GINA 2017			0.570
Mild/moderate (step1–3)	27 (36.5)	56 (32.7)
Severe (step 4–5)	47 (63.5)	115 (67.3)

Notes:

a All data expressed as n (%) unless otherwise indicated.

b Data described as mean ± SD.

Abbreviation: GINA, Global Initiative for Asthma.

Table 3 MAFs and HWE of the included genetic markers

Gene	SNP_ID	Controlled asthma		Uncontrolled asthma
		MAF	P-value	MAF	P-value
ADRB2	rs1042713 G/A	0.270	0.73	0.362	0.52
	rs1042714 C/G	0.354	0.31	0.247	0.96
ADH5	rs1154400 T/C	0.326	0.37	0.247	0.96
ARG1	rs2781659 A/G	0.425	0.58	0.404	0.14
CRHR1	rs1876828 G/A	0.212	0.23	0.213	0.47
	rs242939 A/G	0.110	0.88	0.135	0.06
	rs242941 G/T	0.356	0.52	0.357	0.23
STIP1	rs2236647 C/T	0.319	0.01	0.411	0.29

Abbreviations: HWE, Hardy–Weinberg Equilibrium; MAF, minor allele frequency; SNP, single-nucleotide polymorphism.

Table 4 Genotypic distributions and allelic associations of the studied SNPs with asthma control

Gene	SNP_ID	Genotype distribution and analysis				Allelic distribution and analysis
		Genotype	Controlled asthma, n (%)	Uncontrolled asthma, n (%)	P-value	Allele	Controlled asthma, n (%)	Uncontrolled asthma, n (%)	P-value	Adjusted P-value
ADRB2	rs1042713	AA	6 (8.1)	20 (12)	0.107	A	40 (27)	121 (36.2)	0.048	NS
		AG	28 (37.8)	81 (48.5)		G	108 (73)	213 (63.8)
		GG	40 (54.1)	66 (39.5)
	rs1042714	GG	11 (15.3)	10 (6)	0.041	G	51 (35.4)	82 (24.7)	0.017	NS
		GC	29 (40.3)	62 (37.4)		C	93 (64.6)	250 (75.3)
		CC	32 (44.4)	94 (56.6)
ADH5	rs1154400	CC	6 (8.3)	16 (9.7)	0.725	C	47 (32.6)	103 (31.2)	0.759	NS
		CT	35 (48.6)	71 (43)		T	97 (67.4)	227 (68.8)
		TT	31 (43.1)	78 (47.3)
ARG1	rs2781659	GG	12 (16.4)	22 (13.6)	0.847	G	62 (42.5)	131 (40.4)	0.678	NS
		GA	38 (52.1)	87 (53.7)		A	84 (57.5)	193 (59.6)
		AA	23 (31.5)	53 (32.7)
CRHR1	rs1876828	AA	5 (6.8)	6 (3.6)	0.361	A	31 (21.2)	71 (21.3)	0.995	NS
		AG	21 (28.8)	59 (35.3)		G	115 (78.8)	263 (78.7)
		GG	47 (64.4)	102 (61.1)
	rs242939	GG	1 (1.4)	6 (3.5)	0.833	G	16 (11)	46 (13.4)	0.449	NS
		GA	14 (19.2)	34 (19.9)		A	130 (89)	296 (86.6)
		AA	58 (79.4)	131 (76.6)
	rs242941	TT	8 (11)	25 (14.9)	0.493	T	52 (35.6)	120 (35.7)	0.983	NS
		TG	36 (49.3)	70 (41.7)		G	94 (64.4)	216 (64.3)
		GG	29 (39.7)	73 (43.4)

Abbreviations: SNP, single-nucleotide polymorphism; NS, not significant.

Figure 1 Genetic haplotype blocks: linkage disequilibrium plot of genotyped polymorphisms in CRHR1 (block 1) and ADRB2 (block 2). Boxes without numbers have D′=1.

Table 5 Association between the formed haplotypes and uncontrolled asthma

Haplotype	Frequency of block	Frequency ratio, % (case:control)	P-value	Adjusted, P-value
Block 1: CRHR1 in chromosome 17 (rs1876828 G/A, rs242939 A/G, and rs242941 G/T)
GAG	0.43	42.6:63.6	0.84	NS
TAG	0.23	22.6:24.4	0.67	NS
GAA	0.21	21.3:21.2	0.98	NS
TGG	0.12	13.1:10.7	0.46	NS
Block 2: ADRB2 in chromosome 5 (rs1042713 G/A and rs1042714 C/G)
GC	0.39	39.2:37.9	0.79	NS
AC	0.33	35.9:27.0	0.055	NS
GG	0.28	24.8:35.0	0.021	NS

Abbreviation: NS, not significant.