Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population

doi:10.3748/wjg.v18.i17.2112

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May 7, 2012 (publication date) through May 23, 2024

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World Journal of Gastroenterology

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1007-9327

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Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA

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World J Gastroenterol. May 7, 2012; 18(17): 2112-2120
Published online May 7, 2012. doi: 10.3748/wjg.v18.i17.2112

Table 1 Primer details for genotyping of single nucleotide polymorphisms from NOD1 and NOD2 genes

SNP ID	PCR 1st primer	PCR 2nd primer	Amplication length (bp)	Extension sequence primer
rs17159048	ACGTTGGATGTCAAGAGGAGGGTATTAGGC	ACGTTGGATGCTGTGTGCTTGGGCAGTAAC	93	TTTGGCAGTAACAGTGACAAG
rs2907749	ACGTTGGATGGCTGTGAAGAACAGCAAATC	ACGTTGGATGCACACAGCAGGTTGTACCAC	99	GTAGGTTGTACCACATACATCC
rs2075820	ACGTTGGATGAAGCGCAGCAGGAAGGCAAA	ACGTTGGATGACCTGCTCTTCAAGCACTAC	90	CACTCCTGCTACCCAGAGCGGGACCCC
rs7789045	ACGTTGGATGAGCAGACACAGACAGGGTTC	ACGTTGGATGTTGAGATTGCTGACTGGTGG	95	GTGGTCTCTTCCAGC
rs2067085	ACGTTGGATGATCAGGTTGCCGATCTTCAC	ACGTTGGATGCCTTTCCTGAGAACTCTGTG	95	GTGCCTCACCCTCTG
rs1861759	ACGTTGGATGTGACATTTCTCTTGGCTTCC	ACGTTGGATGTGATGTGAAGGAATTCCAGG	100	AAGACACGACACCTTTGGC
rs3135500	ACGTTGGATGGGCCATGTTGTCTATAAGAG	ACGTTGGATGGATGTGTGAAAACTGGTTAA	99	ATTTGTGAAAACTGGTTAATATTTATAG
rs7205423	ACGTTGGATGCTTGGCTCCAGCCCATTTTG	ACGTTGGATGTATGGCTGCTGCAGGAAATG	99	CACAAATTATCCCCTTATAGTC

SNP: Single nucleotide polymorphism; PCR: Polymerase chain reaction.

Table 2 Baseline clinical characteristics of cases and controls n (%)

	GC group (n = 296)	GA group (n = 160)	P¹
Sex			0.455
Male	222 (75.0)	125 (78.1)
Female	74 (25.0)	35 (21.9)
Helicobacter pylori infection			0.946
Positive	221 (74.7)	119 (74.4)
Negative	75 (25.3)	41 (25.6)
Age (yr)			0.193
≤ 55	131 (43.9)	81 (50.6)
> 55	165 (56.1)	79 (49.4)
Histological type
Intestinal	129 (43.6)
Diffuse	125 (42.2)
Unknown	42 (14.2)

¹Two-sided χ² test. GC: Gastric cancer group; GA: Gastritis group.

Table 3 Adjusted odds ratios for gastric cancer associated with NOD1 and NOD2 polymorphisms

Gene	rsID	Chr	1¹	2¹	GC group	GA group	AOR² (95% CI)
							Heterozygote	Homozygote	Dominant	Recessive
					11/12/22	11/12/22
NOD1	rs17159048	7	G	T	1/62/233	3/38/118³	0.82 (0.52-1.31)	/	0.78 (0.49-1.22)	/
	rs2907749	7	G	A	23/117/156	22/62/76	0.92 (0.61-1.39)	0.50 (0.26-0.95)^a	0.81 (0.55-1.19)	0.52 (0.28-0.96)^a
	rs2075820	7	A	G	32/118/145³	12/78/68³	0.70 (0.47-1.06)	1.27 (0.62-2.64)	0.78 (0.53-1.16)	1.51 (0.75-3.04)
	rs7789045	7	T	A	65/126/105	21/67/72	1.30 (0.85-1.99)	2.14 (1.20-3.82)^a	1.50 (1.01-2.22)^a	1.87 (1.09-3.20)^a
NOD2	rs2067085	16	G	C	0/46/250	0/24/136	1.04 (0.61-1.78)	/	/	/
	rs1861759	16	C	A	8/69/219	3/43/114	0.79 (0.50-1.23)	1.29 (0.33-4.97)	0.82 (0.53-1.27)	/
	rs3135500	16	A	G	16/111/169	12/51/97	1.22 (0.80-1.85)	0.73 (0.33-1.61)	1.13 (0.76-1.67)	0.68 (0.31-1.47)
	rs7205423	16	G	C	20/135/141	14/61/85	1.31 (0.87-1.96)	0.82 (0.39-1.72)	1.22 (0.82-1.79)	0.72 (0.35-1.48)

¹"1"designates the minor allele,"2"designates the major allele;

²ORs were adjusted for the covariates (age, sex and Helicobacter pylori infection);

³One or two subjects failed to be genotyped. GC: Gastric cancer group; GA: Gastritis group.

^aP < 0.05, GC vs GA.

Table 4 Association of the risk single nucleotide polymorphisms in NOD1and NOD2 with two major gastric cancer types and Helicobacter pylori infection status

Type	Genotype			Heterozygote		Homozygote		Dominant model		Recessive model
	AA¹	Aa	aa	AOR² (95% CI)	P	AOR (95% CI)	P	AOR (95% CI)	P	AOR (95% CI)	P
NOD1 rs2907749 risk allele:A
Diffuse 125 cases	68	49	8	2.24 (0.91-5.53)	0.08	2.66 (1.10-6.44)	0.03^a	2.47 (1.05-5.81)	0.04^a	1.39 (0.86-2.24)	0.18
Intestinal 129 cases	66	52	11	1.61 (0.71-3.67)	0.26	1.58 (0.71-3.55)	0.27	1.59 (0.73-3.46)	0.24	1.09 (0.68-1.75)	0.72
160 controls	91	61	8	/	/	/	/	/	/	/	/
NOD1 rs2075820 risk allele:G
Diffuse 125 cases	60	55	13	0.45 (0.19-1.07)	0.07	0.82 (0.36-1.90)	0.65	0.63 (0.28-1.41)	0.26	1.55 (0.96-2.51)	0.08
Intestinal 128 cases	68	41	16	0.54 (0.22-1.31)	0.17	0.77 (0.32-1.85)	0.56	0.65 (0.28-1.51)	0.32	1.29 (0.79-2.08)	0.31
158 controls	68	78	12	/	/	/	/	/	/	/	/
HP⁺ 220 cases	119	78	23	0.39 (0.16-0.99)	0.05	0.674 (0.27-1.68)	0.40	0.53 (0.22-1.28)	0.16	1.47 (0.93-2.31)	0.10
HP⁺ diffuse 93 cases	56	27	10	0.38 (0.13-1.13)	0.08	0.85 (0.29-2.46)	0.76	0.60 (0.21-1.70)	0.34	1.89 (1.07-3.32)	0.03^a
HP⁺ 117 controls	52	58	7	/	/	/	/	/	/	/	/
NOD1 rs7789045 risk allele:T
Diffuse 125 cases	32	51	42	1.36 (0.79-2.33)	0.26	2.97 (1.49-5.95)	0.00^a^b	1.719 (1.045-2.828)	0.03^a	2.53 (1.35-4.74)	0.00^a^b
Intestinal 129 cases	22	60	47	1.39 (0.83-2.32)	0.21	1.55 (0.76-3.16)	0.23	1.42 (0.88-2.31)	0.15	1.31 (0.67-2.53)	0.43
160 controls	20	85	55	/	/	/	/	/	/	/	/
HP⁺ 221 cases	56	86	79	0.99 (0.60-1.62)	0.96	2.05 (1.07-3.94)	0.03^a	1.24 (0.79-1.97)	0.35	2.06 (1.13-3.76)	0.02^a
HP⁺ diffuse 93 cases	28	34	31	1.06 (0.56-2.01)	0.87	3.00 (1.38-6.53)	0.01^a^b	1.50 (0.84-2.69)	0.17	2.91 (1.45-5.87)	0.00^a^b
HP⁺ 119 controls	17	53	49	/	/	/	/	/	/	/	/
NOD2 rs3135500 risk allele:G
HP⁺ 221 cases	132	79	10	2.65 (1.02-6.89)	0.05^a	2.20 (0.88-5.51)	0.091	2.35 (0.96-5.79)	0.06	0.98 (0.62-1.55)	0.92
HP⁺ 119 controls	73	35	11	/	/	/	/	/	/	/	/
NOD2 rs7205423 risk allele:C
HP⁺ 221 cases	112	97	12	2.52 (1.05-6.04)	0.04^a	2.26 (0.96-5.35)	0.06	2.38 (1.03-5.48)	0.04^a	1.04 (0.66-1.63)	0.88
HP⁺ 119 controls	61	45	13	/	/	/	/	/	/	/	/

¹Genotypes are shown as AA for risk allele homozygotes, Aa for heterozygotes and aa for the nonrisk allele homozygotes;

²ORs were adjusted for the covariates (age, sex and/or Helicobacter pylori infection).

^aP < 0.05,

^bP < 0.01, cases vs controls.

Table 5 Frequencies of haplotype of NOD1

Haplotype¹	Frequency		P	P corrected²
	GC (n = 296)	GA (n = 160)
AGT	0.42	0.33	0.01^a	0.04
AAA	0.29	0.32	0.37	0.84
GGA	0.25	0.32	0.02^a	0.08
GAA	0.02	< 0.01	0.05	0.23
AGA	0.01	0.01	0.55	0.96

¹The order of the haplotype is rs2907749, rs2075820 and rs7789045;

²Corrected by 10 000 times permutation test. GC: Gastric cancer group; GA: Gastritis group.

^aP < 0.05, GC vs GA.

Table 6 Associations of NOD1 diplotypes and gastric cancer risk n (%)

Diplotype	GC (n = 296)	GA (n = 160)	AOR¹ (95% CI)	P
AGT/AAA	58 (20)	38 (24)	1
AAA/GGA	47 (16)	35 (22)	0.87 (0.48-1.59)	0.65
AGT/GGA	54 (18)	25 (16)	1.45 (0.77-2.74)	0.25
AGT/AGT	63 (21)	21 (13)	1.98 (1.04-3.80)	0.04^a
GGA/GGA	22 (7)	20 (13)	0.72 (0.34-1.50)	0.38
AAA/AAA	30 (10)	12 (8)	1.69 (0.76-3.72)	0.20
Others	22 (7)	9 (6)	1.58 (0.65-3.81)	0.31

¹ORs were adjusted for the covariates (age, sex and Helicobacter pylori infection). GC: Gastric cancer group; GA: Gastritis group.

^aP < 0.05, GC vs GA.

Table 7 Associations of NOD1 diplotypes and gastric cancer with two major types and Helicobacter pylori infection status

	Diplotype
	AGT/AAA	AAA/GGA	AGT/GGA	AGT/AGT	GGA/GGA	AAA/AAA	Others
HP⁺ GC (n = 221)	34 (15)	35 (16)	41 (19)	54 (24)	18 (8)	22 (10)	17 (8)
HP⁺ GA (n = 119)	32 (27)	22 (18)	18 (15)	17 (14)	16 (13)	7 (6)	7 (6)
AOR¹ (95% CI)	1	1.49 (0.72-3.08)	2.14 (1.01-4.51)^a	3.07 (1.47-6.41)^a	1.09 (0.47-2.53)	2.96 (1.10-7.92)^a	2.44 (0.89-6.71)
P		0.28	0.05^a	0.00²^a^b	0.83	0.03^a	0.08
Diffuse GC (n = 125)	21 (17)	17 (14)	26 (21)	30 (24)	8 (6)	16 (13)	7 (6)
GA (n = 160)	38 (24)	35 (22)	25 (16)	21 (13)	20 (13)	12 (8)	9 (6)
AOR (95% CI)	1	0.84 (0.38-1.88)	1.66 (0.76-3.61)	2.56 (1.17-5.58)^a	0.66 (0.24-1.77)	2.01 (0.78-5.16)	1.33 (0.43-4.14)
P		0.68	0.20	0.02^a	0.41	0.15	0.62
Intestinal GC (n = 129)	29 (23)	22 (17)	25 (19)	22 (17)	11 (9)	12 (9)	8 (6)
GA (n = 160)	38 (24)	35 (22)	25 (16)	21 (13)	20 (13)	12 (8)	9 (6)
AOR (95% CI)	1	0.83 (0.40-1.73)	1.64 (0.76-3.54)	1.43 (0.65-3.14)	0.84 (0.34-2.06)	1.62 (0.619-4.26)	1.13 (0.38-3.34)
P		0.62	0.20	0.38	0.69	0.32	0.83
HP⁺ diffuse GC (n = 93)	12 (13)	13 (14)	19 (20)	26 (28)	7 (8)	10 (11)	6 (7)
HP⁺ GA (n = 119)	32 (27)	22 (19)	18 (15)	17 (14)	16 (13)	7 (6)	7 (6)
AOR (95% CI)	1	1.42 (0.53-3.76)	2.36 (0.91-6.08)	4.02 (1.61-10.05)^a	1.09 (0.35-3.38)	3.12 (0.94-10.40)	2.30 (0.63-8.44)
P		0.48	0.08	0.00²^a^b	0.88	0.06	0.21

¹ORs were adjusted for the covariates (age, sex and/or Helicobacter pylori infection);

²Remained significant after Bonferroni adjustment for multiple comparisons. GC: Gastric cancer group; GA: Gastritis group.

^aP < 0.05,

^bP < 0.01, GC vs GA.

Citation: Wang P, Zhang L, Jiang JM, Ma D, Tao HX, Yuan SL, Wang YC, Wang LC, Liang H, Zhang ZS, Liu CJ. Association of NOD1 and NOD2 genes polymorphisms with Helicobacter pylori related gastric cancer in a Chinese population. World J Gastroenterol 2012; 18(17): 2112-2120
URL: https://www.wjgnet.com/1007-9327/full/v18/i17/2112.htm
DOI: https://dx.doi.org/10.3748/wjg.v18.i17.2112