Association between interleukin-21 gene rs907715 polymorphism and gastric precancerous lesions in a Chinese population

Table 1 Probe primary information for genotyping interleukin-21 gene polymorphisms

Primer	Type	Primer sequences, 5′→3′
rs907715	F	5′-ATAGATGAGGAAAGTGAGATC-3′
	R	5′- CTTTGCTTATTTGATATATTCC-3′
rs2221903	F	5′-GGACCACATATTGCCAG ACAC-3′
	R	5′-GACACTGACGCCCATATTGAT-3′
rs12508721	F	5′-ATGGGACTAAAGT CAAGGTG-3′
	R	5′-AGATGGCTTCTAGAGTCTGG-3′

Table 2 Demographic and lifestyle characteristics of participants in different regions

Characteristic	North		Middle		South		Total
	n = 742	44.3 (%)	n = 488	29.2 (%)	n = 444	26.5 (%)	n = 1674	100 (%)
Gender
Female	464	62.5	128	26.2	136	30.6	728	43.5
Male	278	37.5	360	73.8	308	69.4	946	56.5
BMI	742	20.0 ± 3.2	488	20.6 ± 2.8	444	20.3 ± 2.2	1674	20.6 ± 2.0
Age in yr	742	52.9 ± 15.1	488	46.3 ± 12.8	444	47.5 ± 15.0	1674	49.8 ± 11.4
< 40	110	36.2 ± 5.4	174	36.9 ± 5.2	76	36.7 ± 3.9	360	35.8 ± 2.9
40-49	220	45.1 ± 4.2	202	44.7 ± 4.5	288	44.8 ± 2.1	710	45.5 ± 2.0
50-59	150	54.6 ± 6.1	28	51.8 ± 1.9	8	54.4 ± 2.5	186	54.2 ± 2.0
≥ 60	262	66.1 ± 5.0	84	68.3 ± 11.1	72	77.0 ± 10.4	418	68.0 ± 8.4
Lifestyle
High salt	230	31.0	112	23.0	56	12.6	398	23.8
Smoking	314	42.3	142	29.1	318	71.6	774	46.2
Drinking	286	38.5	116	23.8	184	41.4	586	35.0
Clinical diagnosis
H. pylori infection	512	69.0	296	60.7	360	81.1	1168	69.8
NAG
None	700	94.3	470	96.3	388	87.4	1558	93.1
Mild	23	3.1	10	2.1	35	7.9	68	4.1
Moderate	16	2.2	6	1.2	17	3.8	39	2.3
Severe	3	0.4	2	0.4	4	0.9	9	0.5
AG
None	722	97.3	438	89.8	408	91.9	1568	93.7
Mild	13	1.8	33	6.8	23	5.1	69	4.1
Moderate	6	0.8	14	2.8	10	2.3	30	1.8
Severe	1	0.1	3	0.6	3	0.7	7	0.4
IM
None	612	82.5	328	67.2	368	82.9	1308	78.1
Mild	87	11.7	104	21.3	48	10.9	239	14.3
Moderate	34	4.6	45	9.2	23	5.1	102	6.1
Severe	9	1.2	11	2.3	5	1.1	25	1.5

Data presented as (mean ± standard deviation). BMI: Body mass index; H. pylori: Helicobacter pylori; NAG: Non-atrophic gastritis; AG: Atrophic gastritis; IM: Intestinal metaplasia.

Table 3 Association between risk factors and gastric precancerous lesions

Risk factors		NAG		AG		IM
		OR (95%CI)	P value	OR (95%CI)	P value	OR (95%CI)	P value
Age		1.09 (0.99-1.03)	0.315	0.90 (0.88-1.01)	0.412	1.01 (0.99-1.02)	0.313
BMI		1.01 (0.93-1.11)	0.421	0.89 (0.78-1.32)	0.587	1.11 (0.98-1.24)	0.134
Gender	Female	-		-		-
	Male	1.52 (0.79-2.14)	0.156	0.91 (0.42-1.83)	0.792	1.30 (0.88-1.91)	0.199
High salt	No	-		-		-
	Yes	2.58 (1.21-4.88)	0.011	0.59 (0.24-1.77)	0.315	1.01 (0.55-1.41)	0.699
H. pylori infection	No	-		-		-
	Yes	0.59 (0.37-1.08)	0.141	0.39 (0.65-0.99)	0.041	0.90 (0.77-1.31)	0.555
Smoking	No	-		-		-
	Yes	2.15 (1.19-4.44)	0.015	1.11 (0.77-2.10)	0.515	1.97 (1.40-2.58)	0.005
Drinking	No	-		-		-
	Yes	1.00 (0.99-1.39)	0.057	0.731 (0.49-1.19)	0.161	0.95 (0.89-1.33)	0.668
Region	South	-		-		-
	Middle	0.33 (0.28-0.51)	0.009	0.71 (0.46-1.99)	0.669	2.95 (1.45-4.33)	0.007
	North	0.55 (0.40-1.01)	0.053	0.33 (0.21-0.83)	0.010	1.41 (0.89-2.01)	0.313

BMI: Body mass index; H. pylori: Helicobacter pylori; NAG: Non-atrophic gastritis; AG: Atrophic gastritis; IM: Intestinal metaplasia.

Table 4 Comparison of the genotype distribution of the IL-21 gene polymorphisms in gastric precancerous lesions

SNPs set	Geno-type	Control (n = 290, %)	NAG (n = 116, %)	AG (n = 106, %)	IM (n = 366, %)	OR1	P1 value	OR2	P2 value	OR3	P3 value	OR4	P4 value	OR5	P5 value
rs907715	TT	70 (24.1)	25 (21.6)	19 (17.9)	63 (17.2)	-		-		-		-		-
	CT	143 (49.3)	53 (45.7)	50 (47.2)	170 (46.5)	1.04 (0.60-1.81)	0.896	1.29 (0.71-2.35)	0.408	1.32 (0.88-1.98)	0.179	1.25 (0.87-1.80)	0.230	1.13 (0.62-1.74)	0.439
	CC	77 (26.6)	38 (32.7)	37 (34.9)	133 (36.3)	1.38 (0.76-2.52)	0.290	1.77 (0.93-3.36)	0.079	1.92 (1.24-2.98)	0.004	1.77 (1.19-2.63)	0.005	1.59 (1.06-2.38)	0.013
	C	220 (75.9)	91 (78.4)	87 (82.1)	303 (82.8)	1.16 (0.69-1.94)	0.578	1.46 (0.83-2.56)	0.190	1.53 (1.04-2.24)	0.028	1.43 (1.02-2.01)	0.039	1.28 (1.01-2.22)	0.044
rs12508721	TT	39 (13.4)	14 (12.1)	18 (17.0)	54 (14.8)	-		-		-		-		-
	CT	151 (52.1)	57 (49.1)	55 (51.9)	178 (48.6)	1.05 (0.53-2.08)	0.885	0.79 (0.42-1.50)	0.467	0.85 (0.54-1.36)	0.498	0.87 (0.57-1.33)	0.525	0.82 (0.55-1.28)	0.618
	CC	100 (34.5)	45 (38.8)	33 (31.1)	134 (36.6)	1.25 (0.62-2.54)	0.529	0.72 (0.36-1.42)	0.335	0.97 (0.60-1.57)	0.895	0.96 (0.62-1.50)	0.863	0.88 (0.59-1.33)	0.879
	C	251 (86.6)	102 (87.9)	88 (83.0)	312 (85.2)	1.13 (0.59-2.17)	0.709	0.76 (0.41-1.40)	0.375	0.90 (0.58-1.40)	0.634	0.91 (0.60-1.36)	0.639	0.83 (0.49-1.19)	0.801
rs2221903	TT	231 (79.7)	90 (77.6)	83 (78.3)	271 (74.0)	-		-		-		-		-
	CT	52 (17.9)	24 (20.7)	21 (19.8)	80 (21.9)	1.19 (0.69-2.04)	0.539	1.12 (0.64-1.98)	0.685	1.31 (0.89-1.94)	0.173	1.25 (0.87-1.79)	0.223	1.08 (0.53-1.55)	0.459
	CC	7 (2.4)	2 (1.7)	2 (1.9)	15 (4.1)	0.73 (0.15-3.60)	0.701	0.80 (0.16-3.91)	0.777	1.83 (0.73-4.56)	0.190	1.41 (0.59-3.41)	0.441	1.19 (0.41-2.87)	0.503
	C	59 (20.3)	26 (22.4)	23 (21.7)	95 (26.0)	1.13 (0.67-1.91)	0.643	1.09 (0.63-1.87)	0.769	1.37 (0.95-1.99)	0.092	1.27 (0.90-1.79)	0.171	1.08 (0.81-1.48)	0.311

OR₁: NAG cases compared with controls; OR₂: AG cases compared with controls; OR₃: IM cases compared with controls; OR₄: Total gastric precancerous lesions cases compared with controls; OR₅: Adjusted by age, gender, BMI, drinking status, smoking status, daily salt intake and region. SNPs: Single nucleotide polymorphisms; NAG: Non-atrophic gastritis; AG: Atrophic gastritis; IM: Intestinal metaplasia.

Table 5 Haplotype analysis of polymorphisms in patients and controls

SNPs	Haplo-type	Control (n = 290, %)	NAG (n = 116, %)	AG (n = 106, %)	IM (n = 366, %)	χ2-1	P1 value	OR1	χ2-2	P2 value	OR2	χ2-3	P3 value	OR3
rs907715| rs12508721	CC	0.496	0.543	0.575	0.571	0.713	0.397	1.20 (0.78-1.86)	1.936	0.164	1.37 (0.88-2.15)	3.612	0.057	1.35 (1.00-1.84)
	CT	0.066	0.060	0.057	0.071	0.037	0.847	1.09 (0.45-2.67)	0.104	0.747	1.17 (0.45-3.01)	0.077	0.781	0.92 (0.50-1.69)
	TC	0.163	0.138	0.047	0.087	0.368	0.544	1.21 (0.66-2.23)	8.984	0.003	3.91 (1.51-10.11)	8.509	0.004	2.02 (1.25-3.26)
	TT	0.275	0.259	0.321	0.271	0.125	0.724	1.09 (0.67-1.78)	0.763	0.382	0.81 (0.50-1.31)	0.024	0.878	1.03 (0.73-1.45)
rs2221903| rs907715	CC	0.128	0129	0.123	0.158	0.002	0.963	0.99 (0.52-1.87)	0.017	0.896	1.05 (0.53-2.06)	1.264	0.264	0.78 (0.50-1.21)
	CT	0.006	0.026	0.019	0.014	2.450	0.118	0.26 (0.04-1.59)	1.113	0.292	0.36 (0.05-2.60)	0.701	0.404	0.50 (0.10-2.60)
	TC	0.434	0.474	0.509	0.484	0.527	0.468	0.85 (0.55-1.31)	1.759	0.185	0.74 (0.47-1.16)	1.571	0.210	0.82 (0.60-1.12)
	TT	0.432	0.371	0.349	0.344	1.244	0.265	1.29 (0.83-2.00)	2.158	0.142	1.41 (0.89-2.24)	5.157	0.023	1.44 (1.05-1.98)

Haplotype of rs907715(C/T), rs2221903 (T/C) and rs12508721(C/T). OR₁: NAG cases compared with controls; OR₂: AG cases compared with controls; OR₃: IM cases compared with controls. SNPs: Single nucleotide polymorphisms; NAG: Non-atrophic gastritis; AG: Atrophic gastritis; IM: Intestinal metaplasia.