Distribution characteristics of N-acetyltransferase-2 genotypes and comparison methods of different genotyping in Chinese population

doi:10.19982/j.issn.1000-6621.20210737

Abstract

Abstract:

Objective: To analyze the distribution characteristics of N-acetyltransferase-2 (NAT2) genotypes and the effectiveness of different genotyping methods in Chinese population. Methods: The literatures containing NAT2 gene polymorphism data of Chinese population were retrieved in Medline, PubMed, Embase, China Science and Technology Journal Database, China National Knowledge Internet, and Wanfang database. The retrieval time limit was from the establishment of the database to December 1, 2021, with the English search words of NAT2, N-acetyltransferase, polymorphism, China or Chinese, etc., and Chinese search words of NAT2, gene polymorphism, China, etc.. Newcastle Ottawa scale (NOS) was used to evaluate the quality and bias risk of the included literature. The NAT2 genotype and allele data in the literature were extracted, the NAT2 genotype database of single study was reconstructed, and the haplotype and diplotype were reconstructed and verified by phase 2.1 software. The NAT2 genotype of the control group in the literature were extracted to construct the NAT2 genotype distribution database of Chinese population, and the distribution characteristics of NAT2 alleles and genotypes were analyzed. Based on the constructed NAT2 genotype database, the efficiency of different NAT2 genotyping panels was evaluated. Results: Through literature retrieval and screening, the results of 10 studies were included. The genotype data in the control group of 4010 individuals were summarized. The overall frequencies of NAT2 fast, intermediate and slow metabolism genotype were 25.79% (1034/4010), 50.87% (2040/4010) and 23.34% (936/4010), respectively, the total frequency of NAT2 non-slow metabolism genotype was 76.66% (3074/4010); the total frequencies of NAT2 fast and slow metabolism alleles were 51.19% (4096/8002) and 48.81% (3906/8002), respectively. Using 3SNP method, the sensitivity and specificity of NAT2 slow metabolism genotype inferring were 99.92% (1249/1250) and 99.81% (4190/4198), and were 100.00% (1484/1484) and 99.92% (3961/3964) in NAT2 fast metabolism genotype inferring. Using 2SNP method, the sensitivity and specificity of in NAT2 slow metabolism genotype inferring were 99.52% (1194/1250)and 98.36% (4129/4198); and in NAT2 fast metabolism genotype inferring were 93.19% (1383/1484) and 96.01% (3806/3964). There was no significant difference in the sensitivity of NAT2 slow metabolism genotypes inferred by 3SNP and 2SNP method (χ²=0.189, P=0.664), and there was high consistency between the two methods (Kappa=0.932). The sensitivity of 3SNP method in inferring of NAT2 fast metabolism genotype was higher than that of 2SNP method (χ²=10.973, P=0.001). Conclusion: Non-slow metabolic genotypes constitute the majority of NAT2 metabolic genotypes in Chinese population, and the efficiency of 3SNP method was better than 2SNP method in inferring of NAT2 genotypes.

Key words: Acetyltransferases, Genotype, Alleles, Population surveillance, China

CLC Number:

R968

WANG Ning, ZHENG Lu-yao, MENG Xiu-juan, LIU Hai-ting, DING Yang-ming, YAO Rong, GUO Shao-chen, LU Yu. Distribution characteristics of N-acetyltransferase-2 genotypes and comparison methods of different genotyping in Chinese population[J]. Chinese Journal of Antituberculosis, 2022, 44(6): 625-634. doi: 10.19982/j.issn.1000-6621.20210737

Figures/Tables 10

等位基因	分类	单体型	广州-2011	北京-2012	上海-2015	长沙-2006	上海-2012	郑州-2009	上海-2016	台北-2016	南宁-2021	上海-2004	合计
*4	R	CTCGAG	157(50.65)	128(59.81)	115(65.34)	178(45.18)	339(55.57)	251(59.20)	521(56.14)	412(55.98)	1737(43.58)	132(58.93)	3970(49.61)
*13	R	TTCGAG	0(0.00)	2(0.93)	3(1.70)	22(5.58)	9(1.48)	2(0.47)	2(0.22)	0(0.00)	66(1.66)	3(1.34)	109(1.36)
*11A	R	CTTGAG	0(0.00)	0(0.00)	0(0.00)	3(0.76)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	3(0.04)
*12A	R	CTCGGG	0(0.00)	4(1.87)	0(0.00)	0(0.00)	0(0.00)	3(0.71)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	7(0.09)
*12B	R	TTCGGG	0(0.00)	0(0.00)	0(0.00)	0(0.00)	4(0.66)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	4(0.05)
*12C	R	CTTGGG	0(0.00)	0(0.00)	0(0.00)	3(0.76)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	3(0.04)
*6A	S	TTCAAG	89(28.71)	34(15.89)	14(7.95)	78(19.80)	138(22.62)	87(20.52)	222(23.92)	184(25.00)	1264(31.71)	46(20.54)	2156(26.94)
*7B	S	TTCGAA	44(14.19)	36(16.82)	35(19.89)	70(17.77)	61(10.00)	63(14.86)	152(16.38)	117(15.90)	745(18.69)	38(16.96)	1361(17.01)
*5B	S	CCTGGG	15(4.84)	0(0.00)	2(1.14)	11(2.79)	21(3.44)	10(2.36)	30(3.23)	20(2.72)	174(4.37)	4(1.79)	287(3.59)
*6B	S	CTCAAG	0(0.00)	0(0.00)	1(0.57)	14(3.55)	32(5.25)	1(0.24)	0(0.00)	3(0.41)	0(0.00)	0(0.00)	51(0.64)
*7A	S	CTCGAA	0(0.00)	5(2.34)	0(0.00)	9(2.28)	6(0.98)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	20(0.25)
*5A	S	CCTGAG	2(0.65)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	7(1.65)	1(0.11)	0(0.00)	0(0.00)	0(0.00)	10(0.12)
*5C	S	CCCGGG	3(0.97)	0(0.00)	0(0.00)	2(0.51)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	5(0.06)
*5D	S	CCCGAG	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	1(0.45)	1(0.01)
*6J	S	TTCAAA	0(0.00)	1(0.47)	6(3.41)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	7(0.09)
*6N	S	TTTAAG	0(0.00)	0(0.00)	0(0.00)	4(1.02)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	4(0.05)
*10^a	S	CTCGAG	0(0.00)	2(0.93)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	2(0.02)
*19^a	S	CTCGAG	0(0.00)	2(0.93)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	0(0.00)	2(0.02)

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发表时间	期刊	单位	研究对象数量	民族	人群构成	NAT2基因多态性检测方法	研究编号
2011年^[18]	中国防痨杂志	广州市胸科医院	155	汉族	结核病患者	PCR测序	广州-2011
2012年^[16]	Clinical and Experimental Pharmacology and Physiology	解放军第309医院	208	不明确	结核病患者	PCR测序	北京-2012
2006年^[4]	Disease Markers	中南大学附属湘雅医院	294	汉族	肺癌患者及健康对照者	PCR-RFLP	长沙-2006
2012年^[20]	Frontiers in Bioscience (Elite edition)	中国科学院上海分院及上海市疾病预防控制中心	336^a	汉族	膀胱癌患者及健康对照者	PCR-RFLP	上海-2012
2015年^[17]	中华传染病杂志	复旦大学附属华山医院和上海交通大学医学院附属同仁医院	108	汉族	结核病患者	PCR测序	上海-2015
2016年^[5]	Oncotarget	华南理工大学等	951^b	不明确	膀胱癌患者及健康对照者	iPLEX Gold Assay	上海-2016
2016年^[23]	Journal of the Chinese Medical Association	中国台湾台北荣民总医院	736	不明确	胃癌患者及健康对照者	SNP特异性PCR	台北-2016
2009年^[19]	Cancer Detection and Prevention	郑州大学第一附属医院	420	汉族	膀胱癌患者及健康对照者	PCR-RFLP	郑州-2009
2021年^[21]	Acta Medica Mediterranea	广西医科大学第一附属医院等	2091	汉族	急性髓系白血病(非M3)患者及健康对照者	SNaPshot	南宁-2021
2004年^[22]	Acta Pharmacologica Sinica	中国科学院上海分院等	163	汉族	老年性痴呆患者及健康对照者	PCR-RFLP	上海-2004

研究编号	研究对象选择	组间可比性	暴露因素测量
广州-2011^a	-	-	-
北京-2012	★★★	★	★★★
长沙-2006	★★★★	★★	★★★
上海-2012	★★★★	★	★★
上海-2015	★★★	-	★★★
上海-2016	★★★★	★	★★★
台北-2016	★★★	★★	★★
郑州-2009	★★★★	★★	★★★
南宁-2021	★★★	★	★★★
上海-2004	★★★★	★	★★★

研究编号	NAT2快代谢基因型	NAT2中间代谢基因型	NAT2慢代谢基因型	合计
广州-2011	36(23.3)	85(54.8)	34(21.9)	155
北京-2012	40(37.4)	54(50.5)	13(12.1)	107
长沙-2006	47(23.9)	112(56.9)	38(19.2)	197
上海-2012	102(33.4)	148(48.5)	55(18.1)	305
上海-2015	36(40.9)	46(52.3)	6(6.8)	88
上海-2016	137(29.0)	258(54.5)^a	78(16.5)	473
上海-2004	37(33.0)	61(54.5)	14(12.5)	112
郑州-2009	72(34.0)	112(52.8)	28(13.2)	212
台北-2016	108(29.3)	199(54.1)	61(16.6)	368
南宁-2021	419(21.0)	965(48.4)	609(30.6)	1993
合计	1034(25.8)	2040(50.9)	936(23.3)	4010

基因型	频数	NAT2实际基因型	6SNP位点多态性	3SNP法推断基因型	2SNP法推断基因型
4/4	1366	R	CC TT CC GG AA GG	R	R
4/12A	13	R	CC TT CC GG AG GG	R	R
4/12B	3	R	CT TT CC GG AG GG	R	I
4/13A	88	R	CT TT CC GG AA GG	R	I
13A/13A	10	R	TT TT CC GG AA GG	R	S
4/11A	4	R	CC TT CT GG AA GG	R	R
4/5A	6	I	CC CT CT GG AA GG	I	I
4/5B	178	I	CC CT CT GG AG GG	I	I
4/5C	6	I	CC CT CC GG AG GG	I	I
4/5D	1	I	CC CT CC GG AA GG	I	I
4/6A	1452	I	CT TT CC AG AA GG	I	I
4/6B	139	I	CC TT CC AG AA GG	I	R
4/6J	8	I	CT TT CC AG AA AG	S	I
4/6N	1	I	CT TT CT AG AA GG	I	I
4/7A	7	I	CC TT CC GG AA AG	I	R
4/7B	838	I	CT TT CC GG AA AG	I	I
基因型	频数	NAT2实际基因型	6SNP位点多态性	3SNP法推断基因型	2SNP法推断基因型
4/10	2	I	CC TT CC GG AA GG	R	R
4/19	1	I	CC TT CC GG AA GG	R	R
6A/11	1	I	CT TT CT AG AA GG	I	I
7A/11A	2	I	CC TT CT GG AA AG	I	R
7A/12B	4	I	CT TT CC GG AG AG	I	I
7A/13A	2	I	CT TT CC GG AA AG	I	I
6A/13	35	I	TT TT CC AG AA GG	I	S
6A/12A	3	I	CT TT CC AG AG GG	I	I
7B/13	18	I	TT TT CC GG AA AG	I	S
5B/13	4	I	CT CT CT GG AG GG	I	S
7B/12C	3	I	CT TT CT GG AG AG	I	I
13/6N	2	I	TT TT CT AG AA GG	I	S
11A/6N	1	I	CT TT TT AG AA GG	I	I
5A/5B	9	S	CC CC TT GG AG GG	S	S
5A/6A	6	S	CT CT CT AG AA GG	S	S
5B/5B	9	S	CC CC TT GG GG GG	S	S
5B/6A	93	S	CT CT CT AG AG GG	S	S
5B/7B	70	S	CT CT CT GG AG AG	S	S
5C/6A	1	S	CT CT CC AG AG GG	S	S
6A/6A	374	S	TT TT CC AA AA GG	S	S
6A/6B	38	S	CT TT CC AA AA GG	S	I
6A/7B	482	S	TT TT CC AG AA AG	S	S
6A/19	1	S	CT TT CC AG AA GG	I	I
6B/6B	2	S	CC TT CC AA AA GG	S	R
6B/7A	4	S	CC TT CC AG AA AG	S	R
6B/7B	4	S	CT TT CC AG AA AG	S	I
6J/7B	1	S	TT TT CC AG AA AA	S	S
7A/7A	1	S	CC TT CC GG AA AA	S	R
7A/7B	6	S	CT TT CC GG AA AA	S	I
7B/7B	149	S	TT TT CC GG AA AA	S	S

3SNP法推断	NAT2基因型频数		敏感度 (%)	特异度 (%)	阳性预测值 (%)	阳性预测值 (%)	准确度 (%)
3SNP法推断	S	R+I	敏感度 (%)	特异度 (%)	阳性预测值 (%)	阳性预测值 (%)	准确度 (%)
S	1249	8	99.92	99.81	99.36	99.98	99.83
R+I	1	4190
合计	1250	4198