SLC22A12 gene polymorphism study on susceptibility to hyperuricemia induced by pyrazinamide

doi:10.19982/j.issn.1000-6621.20220315

Abstract

Abstract:

Objective: To investigate the correlation between SLC22A12 gene polymorphism and hyperuricemia induced by pyrazinamide in patients with pulmonary tuberculosis. Methods: A total of 514 patients with pulmonary tuberculosis who had received an intensive regimen containing pyrazinamide in the Third People’s Hospital of Kunming from January 2019 to March 2021 were collected. A total of 294 patients with hyperuricemia were selected as the elevated uric acid group and 220 patients without hyperuricemia were selected as the normal uric acid group. The SNP Sequenom MassARRAY genotyping was used to detect the polymorphisms of rs11602903, rs559946, rs475688 and rs476037 in SLC22A12 gene, and logistic regression model was used to analyze the correlation between the the polymorphisms of related loci and hyperuricemia induced by pyrazinamide. Results: After 4-week treatment with pyrazinamide, the serum uric acid in the elevated uric acid group ((648.32±109.23) μmol/L) was significantly higher than that in the normal uric acid group ((319.14±52.64) μmol/L), and the difference was statistically significant (t=-15.425,P=0.000). Logistic regression model was used to analyze the correlation between the genotypes and alleles of each locus and the occurrence of hyperuricemia in the elevated uric acid group and the normal uric acid group. The results showed that the rs475688 TC (50.3% (148/294) vs. 44.1% (97/220)), TT genotype (21.8% (64/294) vs. 6.4% (14/220)) and T allele (46.9% (276/588) vs. 28.4% (125/440)) of patients in the normal group had a significantly increased risk of hyperuricemia after taking pyrazinamide (OR (95%CI) were 2.028 (1.381-2.978), 6.077 (3.187-11.586), 2.229 (1.714-2.900)). The risk of hyperuricemia was significantly reduced in patients with TA (32.3% (95/294) vs. 50.0% (110/220)), TT genotype (4.1%(12/294) vs. 8.2% (18/220)) and T allele (20.2% (119/588) vs. 33.2% (146/440)) of rs11602903 and TC (32.7% (96/294) vs. 45.5% (100/220)), T allele (20.4% (120/588) vs. 26.4% (116/440)) of rs559946 (OR (95%CI) were 0.425 (0.293-0.616), 0.328 (0.152-0.710), 0.511 (0.385-0.678); 0.578 (0.401-0.833), 0.716 (0.535-0.959), respectively). Conclusion: The rs11602903 and rs559946 polymorphisms of SLC22A12 gene may be related to the reduction of pyrazinamide-induced hyperuricemia. The rs475688 polymorphism may increase the risk of pyrazinamide-induced hyperuricemia.

Key words: Genotype, Polymorphism, single nucleotide, Drug toxicity, Disease susceptibility, Pyrazinamide

CLC Number:

Peng Jiangli, Chen Jie, Chen Yonggang, Wang Lu, Li Na, Luo Ji, Han Yi, Yu Mingli, Zhu Jiangchun. SLC22A12 gene polymorphism study on susceptibility to hyperuricemia induced by pyrazinamide[J]. Chinese Journal of Antituberculosis, 2023, 45(2): 151-158. doi: 10.19982/j.issn.1000-6621.20220315

Figures/Tables 6

组别	例数	尿酸(μmol/L, $x ˉ$ ±s)		血尿素氮(mmol/L, $x ˉ$ ±s)		血肌酐(μmol/L, $x ˉ$ ±s)
组别	例数	服用前	服用4周	服用前	服用4周	服用前	服用4周
尿酸升高组	294例	310.77±48.21	648.32±109.23	3.85±0.72	4.16±0.91	60.94±15.21	62.52±14.11
尿酸正常组	220例	312.35±47.62	319.14±52.64	3.89±0.67	3.92±0.83	58.42±16.15	59.67±15.43
t值		0.443	-15.425	0.622	-1.228	-1.640	-1.038
P值		0.658	0.000	0.534	0.265	0.102	0.304

基因	β值	s $x ˉ$ 值	Wald χ²值	P值	OR(95%CI)值
rs11602903
AA	-	-	-	-	1.000
TA	0.174	0.065	5.527	0.018	0.425(0.293~0.616)
TT	-4.263	2.142	6.752	0.005	0.328(0.152~0.710)
A	-	-	-	-	1.000
T	-4.998	2.313	6.042	0.027	0.511(0.385~0.678)
rs559946
CC	-	-	-	-	1.000
TC	-0.561	0.314	3.425	0.003	0.578(0.401~0.833)
TT	-0.051	0.314	0.125	0.829	0.903(0.358~2.277)
C	-	-	-	-	1.000
T	-0.574	0.311	3.972	0.025	0.716(0.535~0.959)
rs475688
CC	-	-	-	-	1.000
TC	-5.276	2.407	5.150	0.033	2.028(1.381~2.978)
TT	-0.537	0.312	3.956	0.042	6.077(3.187~11.586)
C	-	-	-	-	1.000
T	0.667	0.307	4.698	0.029	2.229(1.714~2.900)
rs476037
GG	-	-	-	-	1.000
AG	0.407	0.423	0.912	0.345	1.191(0.829~1.712)
AA	0.439	0.472	0.725	0.389	1.367(0.670~2.790)
G	-	-	-	-	1.000
A	-0.124	0.221	1.613	0.288	1.156(0.885~1.511)

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位点	正向PCR引物序列	反向PCR引物序列	UEP单碱基延伸引物序列
rs11602903	ACGTTGGATGATTGGGCACACC GAACCTG	ACGTTGGATGACTCACCTGCTGT GGTTGG	gcgaTTTGCTGTTACCCTGTCCT GAG
rs559946	ACGTTGGATGAAAACTTAGGCC TCCCCAAG	ACGTTGGATGAAAGTTTAACCC GCGTTGAG	ttCCCGCGTTGAGGCAGGC
rs475688	ACGTTGGATGGAGAGTGGAAGG TAAAGGTC	ACGTTGGATGAGCACGTCTACC AAGGAAAG	tgagcACCAGGAGGGGTGCCTTG
rs476037	ACGTTGGATGTTAAGTGGAGTC GGTCAGGG	ACGTTGGATGTTACCCAGAAGC CCTGTAAG	cagtCCTCAGCCACCTGCCC

位点	尿酸升高组 (294例)	尿酸正常组 (220例)	χ²值	P值	位点	尿酸升高组 (294例)	尿酸正常组 (220例)	χ²值	P值
rs11602903					rs475688
基因型			24.499	0.000	基因型			36.589	0.000
AA	187(63.6)	92(41.8)			CC	82(27.9)	109(49.5)
TA	95(32.3)	110(50.0)			TC	148(50.3)	97(44.1)
TT	12(4.1)	18(8.2)			TT	64(21.8)	14(6.4)
等位基因			22.038	0.000	等位基因			36.320	0.000
A	469(79.8)	294(66.8)			C	312(53.1)	315(71.6)
T	119(20.2)	146(33.2)			T	276(46.9)	125(28.4)
rs559946					rs476037
基因型			8.786	0.012	基因型			1.295	0.523
CC	186(63.3)	112(50.9)			GG	125(42.5)	104(47.3)
TC	96(32.7)	100(45.5)			AG	146(49.7)	102(46.4)
TT	12(4.0)	8(3.6)			AA	23(7.8)	14(6.3)
等位基因			5.047	0.025	等位基因			1.130	0.288
C	468(79.6)	324(73.6)			G	396(67.3)	310(70.4)
T	120(20.4)	116(26.4)			A	192(32.7)	130(29.6)