The association between cervical lesions of different grades and lncRNA HOTTIP and H19 single nucleotide polymorphisms

doi:10.19401/j.cnki.1007-3639.2022.04.005

Abstract

Abstract:

Background and purpose: Both HOTTIP and H19 are members of long non-coding RNA(lncRNA). They have been found to play an important role in the occurrence, development and migration of tumors. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of HOTTIP rs2067087, H19 rs2839698 and H19 rs2107425 and the risk of cervical lesions of different grades. Methods: The peripheral venous blood and related clinical data of 345 cases of cervical lesions were collected from Nov. 2018 to Dec. 2020 in Yancheng No.1 People's Hospital, including 220 cases of cervical intraepithelial neoplasia (CIN) and 125 cases of cervical cancer (CC). Three hundred and sixty patients without cervical lesions hospitalized during the same period were selected as the control. TaqMan real-time fluorescence quantitative polymerase chain reaction (RTFQPCR) was used to genotype the HOTTIP SNP rs2067087, H19 SNP rs2839698 and rs2107425 in the two groups, and χ² test and unconditional logistic regression were used to analyze the association of the three SNP loci with cervical lesions of different grades. Results: Compared with the control group, there were significant differences in genotype distribution of HOTTIP rs2067087 and H19 rs2839698 in patients with cervical lesions. In the recessive model, the frequency of cervical lesions in patients with HOTTIP rs2067087 GG genotype increased by 52.2% (95% CI: 1.021-2.269, P<0.05). Stratified analysis showed that GG genotype at this locus mainly increased the risk of CIN (OR =1.730, 95% CI: 1.117-2.680, P<0.05); Stratified analysis showed that the GG genotype at this locus mainly increased the risk of CIN (OR=1.730, 95% CI:1.117-2.680, P<0.05). Compared with CC+CT genotype, the risk of cervical cancer in patients with H19 rs2839698 TT genotype was reduced by 70.8% (95% CI: 0.087-0.976, P<0.05). No correlation was found between H19 rs2107425 and cervical lesions of different grades (P>0.05). Conclusion: HOTTIP rs2067087 SNP is associated with different levels of cervical lesions, and the GG genotype may be a risk factor for CIN; H19 rs2839698 SNP is associated with the risk of cervical cancer, and the TT genotype may be a protective factor for cervical cancer.

Key words: Cervical lesions, Cervical cancer, HOTTIP, H19, Single nucleotide polymorphism, Association

CLC Number:

R737.33

WANG Chuntao, GE Anxing, WU Hongyan, ZHANG Xueyan, YANG Sheng, YUAN Hongxiang, CHENG Yanping, FENG Yanlu, LU Xinyuan, LIANG Geyu. The association between cervical lesions of different grades and lncRNA HOTTIP and H19 single nucleotide polymorphisms[J]. China Oncology, 2022, 32(4): 324-334.

Figures/Tables 7

Fig. 1

Tab. 1

Tab. 2

Tab. 3

Tab. 4

Distribution of genotype and allele frequency of HOTTIP rs2067087, H19 rs2839698, rs2107425 among CIN group, cervical cancer group and control group"

Genotype	Controls n (%)	CIN n (%)	P value	OR (95% CI)	CC, n %	P value	OR (95% CI)
HOTTIP rs2067087
Codominant
CC	133 (36.9)	75 (34.1)		1.000	35 (28.0)		1.000
CG	177 (49.2)	97 (44.1)	0.882	0.972 (0.667-1.415)	70 (56.0)	0.085	1.503 (0.945-2.390)
GG	50 (13.9)	48 (21.8)	0.032	1.702 (1.046-2.770)	20 (16.0)	0.199	1.520 (0.803-2.878)
Dominant
CC	133 (36.9)	75 (34.1)		1.000	35 (28.0)		1.000
CG+GG	227 (63.1)	145 (65.9)	0.487	1.133 (0.797-1.610)	90 (72.0)	0.071	1.507 (0.965-2.352)
Recessive
CC+CG	310 (86.1)	172 (78.2)		1.000	105 (84.0)		1.000
GG	50 (13.9)	48 (21.8)	0.014	1.730 (1.117-2.680)	20 (16.0)	0.563	1.181 (0.672-2.075)
Allele
C	443 (61.5)	247 (56.1)		1.000	140 (56.5)		1.000
G	277 (38.5)	193 (43.9)	0.070	1.250 (0.982-1.590)	108 (43.5)	0.159	1.234 (0.921-1.653)
H19 rs2839698
Codominant
CC	195 (54.2)	117 (53.2)		1.000	62 (49.6)		1.000
CT	137 (38.1)	84 (38.2)	0.905	1.022 (0.686-1.396)	60 (48.0)	0.131	1.377 (0.908-2.090)
TT	28 (7.8)	19 (8.6)	0.700	1.131 (0.605-2.115)	3 (2.4)	0.082	0.337 (0.099-1.147)
Dominant
CC	195 (54.2)	117 (53.2)		1.000	62 (49.6)		1.000
CT+TT	165 (45.8)	103 (46.8)	0.817	1.040 (0.743-1.456)	63 (50.4)	0.378	1.201 (0.799-1.805)
Recessive
CC+CT	332 (92.2)	201 (91.4)		1.000	122 (97.6)		1.000
TT	28 (7.8)	19 (8.6)	0.713	1.121 (0.610-2.059)	3 (2.4)	0.046	0.292 (0.087-0.976)
Allele
C	527 (73.2)	318 (72.3)		1.000	184 (73.6)		1.000
T	193 (26.8)	122 (27.7)	0.732	1.048 (0.803-1.367)	66 (26.4)	0.901	0.979 (0.707-1.357)
H19 rs2107425
Codominant
CC	120 (33.3)	66 (30.0)		1.000	48 (38.4)		1.000
CT	168 (46.7)	117 (53.2)	0.226	1.266 (0.864-1.855)	56 (44.8)	0.428	0.833 (0.531-1.308)
TT	72 (20.0)	37 (16.8)	0.789	0.934 (0.568-1.536)	21 (16.8)	0.293	0.729 (0.404-1.316)
Dominant
CC	120 (33.3)	66 (30.0)		1.000	48 (38.4)		1.000
CT+TT	240 (66.7)	154 (70.0)	0.404	1.167 (0.812-1.676)	77 (61.6)	0.305	0.802 (0.526-1.223)
Recessive
CC+CT	288 (80.0)	183 (83.2)		1.000	104 (83.2)		1.000
TT	72 (20.0)	37 (16.8)	0.342	0.809 (0.522-1.253)	21 (16.8)	0.434	0.808 (0.473-1.380)
Allele
C	408 (56.7)	249 (56.6)		1.000	152 (60.8)		1.000
T	312 (43.3)	191 (43.4)	0.980	1.003 (0.790-1.274)	98 (39.2)	0.255	0.843 (0.629-1.131)

Tab. 4

Tab. 5

Tab. 6

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Age/year	Genotype	Controls n (%)	Cases n (%)	P value	OR	95 % CI
HOTTIP rs2067087
≤50	Dominant
	CG+GG	108 (64.7)	123 (66.5)		1.000
	CC	59 (35.3)	62 (33.5)	0.720	0.923	0.594-1.433
	Recessive
	CC+CG	139 (83.2)	145 (78.4)		1.000
	GG	28 (16.8)	40 (21.6)	0.250	1.369	0.801-2.341
>50	Dominant
	CG+GG	119 (61.7)	112 (70.0)		1.000
	CC	74 (38.3)	48 (30.0)	0.102	0.689	0.441-1.076
	Recessive
	CC+CG	171 (88.6)	132 (82.5)		1.000
	GG	22 (11.4)	28 (17.5)	0.104	1.649	0.902-3.013
H19 rs2839698
≤50	Dominant
	CC	94 (56.3)	96 (51.9)		1.000
	CT+TT	73 (43.7)	89 (48.1)	0.409	1.194	0.784-1.817
	Recessive
	CC+CT	157 (94.0)	171 (92.4)		1.000
	TT	10 (6.0)	14 (7.6)	0.558	1.285	0.555-2.977
>50	Dominant
	CC	101 (52.3)	83 (51.9)		1.000
	CT+TT	92 (47.7)	77 (48.1)	0.932	1.018	0.670-1.549
	Recessive
	CC+CT	175 (90.7)	152 (95.0)		1.000
	TT	18 (9.3)	8 (5.0)	0.127	0.512	0.216-1.210
H19 rs2107425
≤50	Dominant
	CC	49 (29.3)	64 (34.6)		1.000
	CT+TT	118 (70.7)	121 (65.4)	0.292	0.785	0.500-1.232
	Recessive
	CC+CT	127 (76.0)	153 (82.7)		1.000
	TT	40 (24.0)	32 (17.3)	0.124	0.664	0.394-1.118
>50	Dominant
	CC	71 (36.8)	50 (31.3)		1.000
	CT+TT	122 (63.2)	110 (68.8)	0.276	1.280	0.821-1.996
	Recessive
	CC+CT	161 (83.4)	134 (83.8)		1.000
	TT	32 (16.6)	26 (16.3)	0.934	0.976	0.554-1.719

Genotype	Cervical adenocarcinoma n (%)	The squamous cell carcinoma of cervix n (%)	χ²	P value	OR	95 % CI
HOTTIP rs2067087			0.007	0.933		0.341-2.685
CC	6 (27.3)	29 (28.2)			1.000
CG+GG	16 (72.2)	74 (71.8)			0.957
H19 rs2839698			0.261	0.610		0.505-3.204
CC	12 (54.5)	50 (48.5)			1.000
CT+TT	10 (45.5)	53 (51.5)			1.272
H19 rs2107425			0.047	0.829		0.346-2.338
CC	8 (36.4)	40 (38.8)			1.000
CT+TT	14 (63.6)	63 (61.2)			0.900