组蛋白去乙酰化酶基因多态性和环境因素对2型糖尿病的影响

程秋婷; 廖日房; 庾永基; 杨萌; 郑莹莹; 陈邓周; 马书丽; 曾转萍

doi:10.16462/j.cnki.zhjbkz.2020.04.004

组蛋白去乙酰化酶基因多态性和环境因素对2型糖尿病的影响

doi: 10.16462/j.cnki.zhjbkz.2020.04.004

1.
510310 广州, 广东药科大学公共卫生学院流行病与卫生统计系
2.
510120 广州, 中山大学附属孙逸仙纪念医院
3.
510850 广州, 花都区第二人民医院

基金项目: 广东省自然科学基金(2018A030313435, 2018A0303130249);广东省中医药卫生管理局基金(20181060);广东省糖脂代谢病流行病学研究(201701)

详细信息

通讯作者:
曾转萍, E-mail:1141518464@qq.com

中图分类号: R587.1
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出版历程
- 收稿日期: 2019-11-08
- 修回日期: 2020-02-11
- 刊出日期: 2020-04-10

Study on the effect of histone deacetylase gene polymorphism and environmental factors on type 2 diabetes mellitus

1.
Department of Epidemiology and Biostatistics, School of Public Health, Guangdong Pharmaceutical University, Guangzhou 510310, China
2.
Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China
3.
The Second People's Hospital of Huadu, Guangzhou 510850, China

Funds: Natural Science Fundation of Guangdong Province(2018A030313435, 2018A0303130249); Project of Administration of Traditional Chinese Medicine of Guangdong Province of China(20181060); Epidemiological Study of Glycolipid Metabolism in Guangdong Province(201701)

More Information

Corresponding author: CAI Li, E-mail:caili5@mail.sysu.edu.cn

摘要

摘要: 目的探讨组蛋白去乙酰化酶(histone deacetylase, HDACs)的3个单核苷酸多态性位点与2型糖尿病(type 2 diabetes mellitus, T2DM)的关联, 以及各位点与环境间交互作用对T2DM易感性的影响, 为T2DM预防和治疗提供依据。方法 2017年在广州市花都区17个行政村和2个社区居委中随机抽取10个村做基线调查后选取T2DM者为病例组, 以同性别、年龄相差不超过5岁和来源于同一行政村为条件, 1:1个体匹配方法匹配对照组。采用条件Logistic回归分析模型分析基因和环境及其交互作用对T2DM的影响。结果共调查499名病例, 平均年龄(61.53±13.08)岁, 男性占37.88%;499名对照的平均年龄(61.48±13.09)岁, 男性占37.88%。甘油三酯(triglyceride, TG)异常(OR=2.410, 95% CI:1.755~3.310, P < 0.001)和总胆固醇(total cholesterol, TC)异常(OR=1.436, 95% CI:1.046~1.972, P=0.025)是T2DM的危险因素。rs72792338 TT+TC基因型携带(OR=0.526, 95% CI:0.349~0.793, P=0.002)是T2DM的保护因素。结论甘油三酯和总胆固醇异常是T2DM的危险因素, rs72792338 TT和TC基因型携带是T2DM的保护因素, 未发现HDACs基因与环境对T2DM的影响存在交互作用。
- 2型糖尿病 /
- HDACs /
- 交互作用
Abstract: Objective To examine whether polymorphisms of histone deacetylase(HDACs) and environment factors can be implicated in type 2 diabetes mellitus(T2 DM), and to provide evidence for the prevention and treatment of T2 DM. Methods In 2017, T2 DM patients and controls were selected from 17 villages in Huadu District, Guangzhou. According the Diagnostic criteria for T2 DM, the case group of T2 DM was matched with control group from the population diagnosed as normal by gender, age no more than 5 years old, and from the same natural village. Conditional logistic regression model was used to analyze the effect of gene and environment and their interaction on T2 DM. Results The average age of 499 cases group were(61.53±13.08) years old, and the average age of 499 controls group were(61.48±13.09) years old. There were no statistic difference between two groups. Furthermore, the two groups were gender-balanced too. In conditional logistic regression model, we found that glycerin trilaurate(TG) abnormalities(OR=2.410, 95% CI: 1.755-3.310, P < 0.001) and cholesterol total(TC) abnormalities(OR=1.436, 95% CI: 1.046-1.972, P=0.025) were risk factors for T2 DM. The subjects carries rs72792338 TC+TT genotype(OR=0.526, 95% CI: 0.349-0.793, P=0.002) had lower the risk to develop T2 DM. Conclusions Abnormal TG and TC are risk factors for T2 DM. Rs72792338 TT and TC genotype carryings decrease the risk of T2 DM.
- Type 2 diabetes mellitus /
- Histone deacetylase /
- Interaction

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表 1 遗传变异基本信息

Table 1. Information of genetic variation

位点	基因	等位基因	最小等位基因频率	功能区	Haploreg-eQTL	Regulome-DB评分
rs72792338	HDAC3	C > T	0.040	intron	-	3a
rs14251	HDAC3	C > T	0.117	Missense	√	5
rs113045253	SIRT1	C > T	0.131	intron	-	3a

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表 2 T2DM影响因素单因素条件Logistic回归分析[n(%)]

Table 2. 2 Conditional Logistic regression analysis of single-factor for the influencing factor of T2DM[ n(%)]

因素	病例组	对照组	OR(95% CI)值	P值
BMI(kg/m²)
正常	300(60.12)	334(66.93)
消瘦	10(2.00)	23(4.61)	0.443(0.194~1.012)	0.054
超重	141(28.26)	103(20.64)	1.674(1.204~2.327)	0.002
肥胖	48(9.62)	39(7.82)	1.427(0.888~2.293)	0.142
吸烟
否	414(82.97)	400(80.16)
是	85(17.03)	99(19.84)	0.754(0.508~1.121)	0.163
饮酒
否	450(90.18)	441(88.38)
是	49(9.82)	58(11.62)	0.804(0.522~1.240)	0.324
高血压
否	282(56.51)	310(62.12)
是	217(43.49)	189(37.88)	1.368(1.018~1.839)	0.038
TC
正常	348(69.74)	387(77.56)
异常	151(30.26)	112(22.44)	1.557(1.153~2.102)	0.004
TG
正常	336(67.33)	417(83.57)
异常	163(32.67)	82(16.43)	2.446(1.793~3.338)	< 0.001
rs72792338
CC	456(91.38)	426(85.37)
TC	38(7.62)	58 (11.62)	0.627(0.411~0.954)	0.029
TT	5(1.00)	15 (3.01)	0.317(0.115~0.874)	0.027
显性模型	-	-	0.565(0.382~0.837)	0.004
隐性模型	-	-	0.333(0.121~0.917)	0.033
加性模型	-	-	0.600(0.432~0.833)	0.002
rs113045253
CC	383(76.76)	374(74.95)
AC	108(21.64)	116(23.25)	0.914(0.684~1.221)	0.543
AA	8(1.60)	9 (1.80)	0.870(0.335~2.261)	0.775
显性模型	-	-	0.911(0.687~1.208)	0.517
隐性模型	-	-	0.889(0.343~2.304)	0.809
加性模型	-	-	0.919(0.712~1.186)	0.515
rs14251
CC	398(79.76)	400(80.16)
AC	94(18.84)	92(18.44)	1.025(0.752~1.399)	0.874
AA	7(1.40)	7 (1.40)	1.006(0.324~3.128)	0.991
显性模型	-	-	1.024(0.756~1.389)	0.877
隐性模型	-	-	1.000(0.323~3.101)	1.000
加性模型	-	-	1.021(0.771~1.350)	0.886

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表 3 T2DM影响因素多因素条件logistic回归分析

Table 3. 3 Analysis of multivariate conditional logistic regression for influencing factors on T2DM

影响因素	β值	S_x	Wald χ²值	OR(95% CI)值	P值
TG
正常				1.000
异常	0.879	0.162	29.545	2.410(1.755~3.310)	< 0.001
TC
正常				1.000
异常	0.362	0.162	4.996	1.436(1.046~1.972)	0.025
rs72792338显性模型
CC				1.000
TC+TT	-0.643	0.210	9.413	0.526(0.349~0.793)	0.002

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表 4 rs72792338和TG, rs72792338和TC对T2DM影响的交互作用分析

Table 4. Analysis of interaction on T2DM between rs72792338 and TG, rs72792338 and TC

影响因素	cOR(95% CI)值	P值	OR(95% CI)值^a	P值^a
rs72792338显性模型	0.603(0.376~0.966)	0.035	0.583(0.362~0.941)	0.027
TG	2.664(1.895~3.745)	< 0.001	2.312(1.620~3.301)	< 0.001
rs72792338显性模型×TG	0.624(0.242~1.608)	0.329	0.634(0.241~1.667)	0.356
rs72792338显性模型	0.557(0.342~0.906)	0.019	0.506(0.305~0.837)	0.008
TC	1.582(1.149~2.180)	0.005	1.387(0.985~1.954)	0.061
rs72792338显性模型×TC	0.989(0.415~2.354)	0.980	1.080(0.432~2.695)	0.870
注:^a表示调整了BMI、血压、TC(或TG)、吸烟和饮酒。

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表 5 基因-基因对T2DM影响的交互作用分析

Table 5. Analysis of interaction between gene and gene on T2DM

因素1	因素2	病例(人)	对照(人)	OR(95% CI)值	RERI(95% CI)值	OR(95% CI)值^a	RERI(95% CI)值^a
rs72792338	rs113045253				0.043(-0.499~0.585)		-0.009(-0.553~0.534)
-	-	365	344	1.000		1.000
+	-	18	30	0.564(0.356~0.896)		0.525(0.323~0.851)
-	+	30	54	0.938(0.692~1.273)		0.980(0.711~1.352)
+	+	86	71	0.546(0.267~1.114)		0.496(0.234~1.052)
rs72792338	rs14251				-0.088(-0.731~0.554)		-0.135(-0.720~0.451)
-	-	361	338	1.000		1.000
+	-	37	62	0.577(0.378~0.879)		0.539(0.345~0.843)
-	+	95	88	1.023(0.743~1.408)		1.010(0.720~1.416)
+	+	6	11	0.511(0.188~1.393)		0.415(0.149~1.156)
rs14251	rs113045253				0.535(-0.316~1.386)		0.586(-0.352~1.524)
-	-	307	294	1.000		1.000
+	-	76	80	0.911(0.645~1.287)		0.873(0.605~1.261)
-	+	91	106	0.826(0.602~1.133)		0.875(0.623~1.228)
+	+	25	19	1.272(0.686~2.359)		1.334(0.694~2.562)
注:-表示野生纯合型, +表示突变基因携带; ^a表示调整了BMI、血压、吸烟、饮酒、TC、TG和rs72792338显性模型。

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