Single nucleotide polymorphisms in cytokine genes and their association with primary Sjögren’s syndrome in Saudi patients: A cross-sectional study

Bashaer Alqahtani; Maha Daghestani; Mohammed A. Omair; Fahidah Alenzi; Esam H. Alhamad; Yusra Tashkandy; Nashwa Othman; Arjumand Warsy; Rabih Halwani

doi:10.15537/smj.2023.44.12.20230490

Article Figures & Data

Tables

View popup
Table 1
- Demographic variables and outcome measures.
Variable Patients with pSS
(n=41)
(mean ± SD) Control
(n=71)
(mean ± SD)
Age 58.76 ± 12.7 48.87^* ± 14.49
ESSDAI 9.95 ± 7.73 -
Disease duration (years) 4.6 ± 2.28 -
ESSDAI: EULAR Sjögren’s syndrome disease activity index,
pSS: Primary Sjögren’s syndrome, SD: standard deviation
↵* p<0.001.

View popup

Table 2

- Supplemental genotype and allele frequencies of cytokine gene polymorphisms in patients with primary Sjögren syndrome (pSS) versus controls

Gene	Variant	Genotype/allele	Patients with pSSn (%)	Control group n (%)	OR (95% CI)	X²	P-value
Interleukin-1 beta (IL-1β)	rs16944	Genotype frequency (pSS=33; HC=60)
		AA	5 (15.2)	13 (21.7)	Reference
		AG	12 (36.4)	19 (31.7)	0.609 (0.173–2.146)	0.596	0.440
		GG	16 (48.5)	28 (46.7)	0.673 (0.203–2.236)	0.418	0.518
		Allele frequency
		A	22 (33.33)	45 (37.5)	Reference
		G	44 (66.7)	75 (62.5)	0.833 (0.443–1.567)	0.320	0.571
	rs1143627	Genotype frequency (pSS=33; HC=55)
		CC	12 (36.4)	9 (16.4)	Reference
		CT	7 (21.2)	29 (52.7)	5.524 (1.672–18.250)	7.856	0.005^*
		TT	14 (42.4)	17 (30.9)	1.619 (0.530–4.946)	0.715	0.398
		Allele frequency
		C	31 (47.0)	47 (42.7)	Reference
		T	35 (53.0)	63 (57.3)	1.187 (0.643–2.193)	0.301	0.583
Interferon regulatory factor 5(IRF5)	rs10488631	Genotype frequency (pSS=32; HC=57)
		TT	18 (56.3)	44 (77.2)	Reference
		TC	5 (15.6)	13 (22.8)	1.064 (0.331–3.421)	0.011	0.918
		CC	9 (28.1)	0 (0.0)	-	-	-
		Allele frequency
		T	41 (64.1)	101 (88.6)	Reference
		C	23 (35.9)	13 (11.4)	0.229 (0.106–0.496)	14.009	<0.001^*
Monocyte chemoattractant protein 1 (MCP-1)	rs1024611	Genotype frequency (pSS=29; HC=65)
		AA	19 (65.5)	35 (53.9)	Reference
		AG	8 (27.6)	16 (24.6)	1.086 (0.393–2.999)	0.025	0.874
		GG	2 (6.9)	14 (21.5)	3.800 (0.780–18.511)	2.731	0.098
		Allele frequency
		A	46 (79.3)	86 (66.3)	Reference
		G	12 (20.7)	44 (33.9)	1.961 (0.943–4.077)	3.254	0.071
B-cell activating factor (BAFF)	rs12583006	Genotype frequency (pSS=35; HC=64)
		TT	14 (40.0)	37 (57.8)	Reference
		TA	14 (40.0)	21 (32.8)	0.568 (0.228–1.416)	1.475	0.225
		AA	7 (20.0)	6 (9.4)	0.324 (0.093–1.134)	3.108	0.078
		Allele frequency
		T	42 (60.0)	95 (74.2)	Reference
		A	28 (40.0)	33 (25.8)	0.521 (0.280–0.969)	4.235	0.040^*
Tumor necrosis factor Superfamily Member 4 (TNFSF4)	rs1234315	Genotype frequency (pSS=32; HC=59)
		CC	12 (37.5)	13 (22.0)	Reference
		CT	12 (37.5)	24 (40.7)	1.846 (0.648–5.259)	1.318	0.251
		TT	8 (25.0)	22 (37.3)	2.538 (0.822–7.836)	2.624	0.105
		Allele frequency
		C	36 (56.3)	50 (42.4)	Reference
		T	28 (43.6)	68 (57.6)	1.749 (0.946–3.232)	3.180	0.075
Interleukin-2 – interleukin-21 gene region (IL-2 – IL-21)	rs6822844	Genotype frequency (pSS=32; HC=58)
		GG	28 (87.5)	49 (84.5)	Reference
		GT	3 (9.4)	9 (15.5)	1.653 (0.412–6.627)	0.503	0.478
		TT	1 (3.1)	0 (0.0)	-	-	-
		Allele frequency
		G	59 (92.2)	107 (92.2)	Reference
		T	5 (7.8)	9 (7.8)	0.993 (0.318–3.099)	0.000	0.990
Tumor necrosis factor-alpha (TNFα)	rs1800629	Genotype frequency (pSS=26; HC=56)
		GG	18 (69.2)	41 (73.2)	Reference
		GA	6 (23.1)	8 (14.3)	0.585 (0.177–1.933)	0.772	0.380
		AA	2 (7.7)	7 (12.5)	1.537 (0.290–8.133)	0.255	0.613
		Allele frequency
		G	42 (80.8)	90 (80.4)	Reference
		A	10 (19.2)	22 (19.6)	1.027 (0.447–2.360)	0.004	0.951
Signal transducer and activator of transcription 4 (STAT4)	rs7574865	Genotype frequency (pSS = 26; HC = 59)
		TT	1 (3.9)	8 (13.6)	Reference
		TG	10 (38.5)	21 (35.6)	0.263 (0.029–2.395)	1.406	0.236
		GG	15 (57.7)	30 (50.9)	0.250 (0.029–2.188)	1.569	0.210
		Allele frequency
		T	12 (23.1)	37 (31.4)	Reference
		G	40 (76.9)	81 (68.8)	0.657 (0.309–1.395)	1.197	0.274

CI: confidence interval, OR: odd ratio, HC: healthy control

↵* p<0.05,

View popup

Table 3

- Association of rs1143627 in the interleukin-1 beta (IL-1β) gene with different autoimmune diseases in populations of different ancestries.

Ref.	Disease	No. (patients/controls)	Associated genotype or allele	OR (95% CI)	P-value	Frequency (patient vs. control)	Ethnicity
[23]	Primary Sjögren syndrome (pSS)	101/106	TT	0.59 (0.31–1.13)	0.027	19.6 vs. 29.2	Japanese
[24]	Rheumatoid arthritis	180/249	TT	1.21 (0.92–1.61)	0.01	0.26 vs. 0.15	Indian
[25]	Systemic lupus erythematosus	50/25	TT	8.27 (1.53–44.61)	<0.01	26 vs. 8	Egyptian
[26]	Alzheimer’s disease	123/120	TT	1.72 (1.13–2.61)	0.010	51 (41.5) vs. 31 (25.8)	Chinese
[27]	Immune thrombocytopenia	118/100	TT	2.33 (1.069–5.09)	0.033	25.43 vs. 19	Indian
			CT	2.044 (1.068–39)	0.034	55.08 vs. 47
			T	1.52 (1.04–2.22)	0.034	52.69 vs. 42.5
[28]	Systemic sclerosis	78/692	TC	2.7 (1.5–5.1)	0.002	62.0 vs. 43.8	Caucasian
[29]	Systemic lupus erythematosus	163/180	CC	0.6 (0.4–0.9)	<0.01	52 (32) vs. 81 (45)	Iranian
[29]	Systemic lupus erythematosus	163/180	CC	0.7 (0.5–0.9)	<0.01	191 (58.6) vs. 247 (68.6)	Iranian
[30]	Coronary artery lesions in Kawasaki disease	719/1401	AA	2.28 (1.32–3.95)	0.003	50 vs. 29	Chinese