双生子多巴胺D3受体基因多态性对儿童体成分的影响

doi:10.16359/j.1000-3193/AAS.2021.0028

摘要/Abstract

摘要：

均衡的体成分构成对维持机体的健康状态具有重要作用,体成分受遗传与环境因素的共同影响。多巴胺参与摄食、运动及认知等活动的调节,多巴胺D3受体（DRD3）对多巴胺神经通路起关键调节作用,进而对摄食功能发挥作用,从而可能对体成分产生影响。为了解遗传与环境因素对双生子儿童体成分的影响,并探讨DRD3基因单核苷酸多态性（SNP）与体成分的相关性,对160对4-12岁双生子肱三头肌皮褶厚度（d₁）、肩胛下皮褶厚度（d₂）、髂前上棘位皮褶厚度（d₃）和体质量（m）进行了测量,计算d₄(d₁+d₂)、d₅(d₂/d₁),体脂率（P_f）、瘦体质量（m_l）;从口腔拭子中提取全基因组DNA;通过Amp FISTR Sino filerPlus试剂盒分析确定卵型;采用SNaPshot技术对DRD3基因4个SNP位点进行检测;使用Mx软件估算各指标遗传度;运用广义估计方程模型分析各指标与DRD3基因SNP的相关性。校正年龄效应后,除个别指标（d₃, m_l）外,男女生指标遗传度（h）学龄前期总体偏低,且某些指标（d₂, d₄, P_f, m_l）的遗传度存在一定的性别差异。d₂分别与rs324029、rs226082存在相关（P<0.05）; d₃分别与rs2134655、rs226082存在相关（P<0.05）;d₅分别与rs2134655、rs167771存在相关（P<0.05）;P_f分别与rs226082、rs167771存在相关（P<0.05）;m_l分别与rs2134655、rs226082、rs167771存在相关（P<0.05）。本研究结果表明,遗传和环境因素对儿童体成分发育均有影响,但遗传效应可能存在一定的发育阶段和性别差异;DRD3基因SNPs与儿童的体成分可能存在一定的相关性。

关键词: 双生子, 多巴胺D3受体基因, 单核苷酸多态性, 遗传度, 体成分

Abstract:

Balanced body composition plays an important role in maintaining the health of the body. Body composition is affected by both genetic and environmental factors. Dopamine is involved in the regulation of food intake, movement and cognition, dopamine D3 receptor (DRD3) plays a key regulatory role in dopamine pathway, and then plays a role in feeding function, thus may affect body composition. In order to understand the influence of genetic and environmental factors on body composition of twins, and to explore the correlation between single nucleotide polymorphism (SNP) of DRD3 gene and body composition, the triceps skinfold (d₁), subscapular skinfold (d₂) and suprailiac skinfold (d₃) and body mass(m) were measured in 160 pairs of twins aged 4-12 years, d₄(d₁+d₂), d₅(d₂/d₁), body fat percentage(P_f), lean body mass(m_l) were calculated. The whole genome DNA was extracted from oral swab. The zygosity was determined by Amp FISTER SinofilerPlus kit. Four SNPs of DRD3 gene were detected by SNapshot technique. The heritability of each index was estimated by Mx software. The association between SNP of DRD3 gene and each index was analyzed by generalized estimating equation (GEE) model. After adjusting for the age effect, except for some indexes (d₃, m_l), the heritability of boys and girls in preschool is generally low, the heritability of some indexes (d₂, d₄, P_f, m_l) showed some gender differences. There were association between d₂ and rs32409, rs226082 (P<0.05), between d₃ and rs2134655, rs226082 (P<0.05), between d₅ and rs2134655, rs167771 (P<0.05), between P_fand rs226082, rs167771 (P<0.05), between m_l and rs2134655, rs226082 and rs167771(P<0.05) respectively. The results showed that both genetic and environmental factors affected the body composition development of children, but there may be some developmental stages and gender differences in genetic effects. SNPs of DRD3 gene may be related to body composition of children.

Key words: Twins, Dopamine D3 receptor gene, Single nucleotide polymorphism, Heritability, Body composition

中图分类号:

Q984

刘晓敏, 乌云达来, 李玉玲. 双生子多巴胺D3受体基因多态性对儿童体成分的影响[J]. 人类学学报, 2022, 41(02): 274-281.

LIU Xiaomin, DALAI Wuyun, LI Yuling. Influence of dopamine D3 receptor gene polymorphism on body composition in twins[J]. Acta Anthropologica Sinica, 2022, 41(02): 274-281.

图/表 2

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指标 Variable	模型 Model	年龄 Age	女Female					男Male					C_ai	χ²	P
指标 Variable	模型 Model	年龄 Age	E_a	E_c	E_e	E_s	h	E_a	E_c	E_e	E_s	h	C_ai	χ²	P
d₁	IV	4-6	0.23	0.50	0.15	0.12	0.27	0.43	0.35	0.22	0.00	0.43	-20.40	11.60	0.77
	IV	7-12	0.62	0.20	0.14	0.05	0.65	0.60	0.15	0.20	0.05	0.63	-21.86	10.13	0.86
d₂	IV	4-6	0.30	0.57	0.12	0.01	0.30	0.47	0.38	0.12	0.04	0.49	-20.45	11.55	0.78
	IV	7-12	0.21	0.35	0.21	0.23	0.27	0.49	0.29	0.07	0.15	0.57	-23.82	8.18	0.94
d₃	IV	4-6	0.37	0.47	0.09	0.06	0.40	0.42	0.41	0.16	0.01	0.42	-14.87	17.14	0.38
	IV	7-12	0.22	0.42	0.15	0.21	0.28	0.40	0.34	0.13	0.13	0.46	-14.53	17.47	0.36
d₄	IV	4-6	0.19	0.60	0.13	0.08	0.21	0.49	0.36	0.14	0.01	0.50	-19.72	12.28	0.72
	IV	7-12	0.39	0.30	0.16	0.15	0.45	0.58	0.23	0.09	0.10	0.65	-23.67	8.33	0.94
d₅	IV	4-6	0.26	0.51	0.17	0.07	0.28	0.16	0.51	0.28	0.05	0.17	-13.33	18.67	0.29
	IV	7-12	0.22	0.30	0.31	0.17	0.27	0.16	0.34	0.41	0.09	0.17	-19.38	12.61	0.70
P_f	IV	4-6	0.18	0.61	0.15	0.07	0.19	0.64	0.24	0.11	0.01	0.65	-17.81	14.19	0.59
	IV	7-12	0.45	0.32	0.17	0.06	0.48	0.63	0.17	0.09	0.11	0.71	-20.15	11.85	0.75
m_l	IV	4-6	0.70	0.00	0.06	0.24	0.92	0.56	0.00	0.06	0.38	0.91	-13.61	18.39	0.30
	IV	7-12	0.15	0.14	0.11	0.59	0.37	0.34	0.14	0.03	0.49	0.66	-15.46	16.55	0.42

指标 Variable	模型 Model	年龄 Age	女Female					男Male					C_ai	χ²	P
指标 Variable	模型 Model	年龄 Age	E_a	E_c	E_e	E_s	h	E_a	E_c	E_e	E_s	h	C_ai	χ²	P
d₁	IV	4-6	0.23	0.50	0.15	0.12	0.27	0.43	0.35	0.22	0.00	0.43	-20.40	11.60	0.77
	IV	7-12	0.62	0.20	0.14	0.05	0.65	0.60	0.15	0.20	0.05	0.63	-21.86	10.13	0.86
d₂	IV	4-6	0.30	0.57	0.12	0.01	0.30	0.47	0.38	0.12	0.04	0.49	-20.45	11.55	0.78
	IV	7-12	0.21	0.35	0.21	0.23	0.27	0.49	0.29	0.07	0.15	0.57	-23.82	8.18	0.94
d₃	IV	4-6	0.37	0.47	0.09	0.06	0.40	0.42	0.41	0.16	0.01	0.42	-14.87	17.14	0.38
	IV	7-12	0.22	0.42	0.15	0.21	0.28	0.40	0.34	0.13	0.13	0.46	-14.53	17.47	0.36
d₄	IV	4-6	0.19	0.60	0.13	0.08	0.21	0.49	0.36	0.14	0.01	0.50	-19.72	12.28	0.72
	IV	7-12	0.39	0.30	0.16	0.15	0.45	0.58	0.23	0.09	0.10	0.65	-23.67	8.33	0.94
d₅	IV	4-6	0.26	0.51	0.17	0.07	0.28	0.16	0.51	0.28	0.05	0.17	-13.33	18.67	0.29
	IV	7-12	0.22	0.30	0.31	0.17	0.27	0.16	0.34	0.41	0.09	0.17	-19.38	12.61	0.70
P_f	IV	4-6	0.18	0.61	0.15	0.07	0.19	0.64	0.24	0.11	0.01	0.65	-17.81	14.19	0.59
	IV	7-12	0.45	0.32	0.17	0.06	0.48	0.63	0.17	0.09	0.11	0.71	-20.15	11.85	0.75
m_l	IV	4-6	0.70	0.00	0.06	0.24	0.92	0.56	0.00	0.06	0.38	0.91	-13.61	18.39	0.30
	IV	7-12	0.15	0.14	0.11	0.59	0.37	0.34	0.14	0.03	0.49	0.66	-15.46	16.55	0.42

指标Variable	DRD3		±σ	B	σ_s	95% Confidence Interval		χ²	P
指标Variable	DRD3		±σ	B	σ_s	Lower limit	Upper limit	χ²	P
d₂	rs324029	GG	6.22±1.05	-0.143	0.067	-0.274	-0.012	4.599	0.032
		GA	6.60±1.07	-0.084	0.082	-0.244	0.076	1.061	0.303
		AA	7.18±1.08	0^a
	rs226082	CC	6.44±1.07	-0.003	0.046	-0.093	0.088	0.003	0.956
		CT	7.12±1.06	0.101	0.041	0.021	0.181	6.086	0.014
		TT	6.42±1.05	0^a
d₃	rs2134655	GG	5.95±1.05	-0.206	0.105	-0.412	0.000	3.851	0.050
		GA	6.57±1.06	-0.080	0.095	-0.265	0.105	0.714	0.398
		AA	6.88±1.09	0^a
	rs226082	CC	6.73±1.11	0.037	0.060	-0.080	0.154	0.392	0.531
		CT	7.48±1.10	0.142	0.047	0.050	0.235	9.106	0.003
		TT	6.48±1.10	0^a
d₅	rs2134655	GG	0.74±1.03	0.185	0.066	0.057	0.313	7.983	0.005
		GA	0.70±1.05	0.122	0.045	0.035	0.209	7.500	0.006
		AA	0.62±1.07	0^a
	rs167771	GG	0.62±1.07	-0.177	0.051	-0.276	-0.078	12.207	0.000
		GA	0.69±1.06	-0.070	0.069	-0.204	0.064	1.037	0.309
		AA	0.74±1.04	0^a
P_f	rs226082	CC	17.62±1.04	0.008	0.012	-0.014	0.031	0.532	0.466
		CT	18.26±1.04	0.024	0.010	0.004	0.044	5.681	0.017
		TT	17.28±1.03	0^a
	rs167771	GG	17.28±1.04	0.011	0.011	-0.010	0.032	1.111	0.292
		GA	19.10±1.06	0.055	0.021	0.014	0.096	6.825	0.009
		AA	16.84±1.03	0^a
m_l	rs2134655	GG	22.17±1.03	-0.120	0.056	-0.229	-0.012	4.712	0.026
		GA	23.80±1.04	-0.052	0.044	-0.138	0.035	1.372	0.236
		AA	25.03±1.06	0^a
	rs226082	CC	23.07±1.05	-0.007	0.038	-0.081	0.067	0.036	0.811
		CT	24.58±1.04	0.055	0.022	0.013	0.097	6.505	0.013
		TT	23.28±1.04	0^a
	rs167771	GG	22.87±1.06	0.012	0.042	-0.071	0.094	0.078	0.831
		GA	25.47±1.05	0.115	0.045	0.028	0.202	6.644	0.008
		AA	22.66±1.04

指标Variable	DRD3		±σ	B	σ_s	95% Confidence Interval		χ²	P
指标Variable	DRD3		±σ	B	σ_s	Lower limit	Upper limit	χ²	P
d₂	rs324029	GG	6.22±1.05	-0.143	0.067	-0.274	-0.012	4.599	0.032
		GA	6.60±1.07	-0.084	0.082	-0.244	0.076	1.061	0.303
		AA	7.18±1.08	0^a
	rs226082	CC	6.44±1.07	-0.003	0.046	-0.093	0.088	0.003	0.956
		CT	7.12±1.06	0.101	0.041	0.021	0.181	6.086	0.014
		TT	6.42±1.05	0^a
d₃	rs2134655	GG	5.95±1.05	-0.206	0.105	-0.412	0.000	3.851	0.050
		GA	6.57±1.06	-0.080	0.095	-0.265	0.105	0.714	0.398
		AA	6.88±1.09	0^a
	rs226082	CC	6.73±1.11	0.037	0.060	-0.080	0.154	0.392	0.531
		CT	7.48±1.10	0.142	0.047	0.050	0.235	9.106	0.003
		TT	6.48±1.10	0^a
d₅	rs2134655	GG	0.74±1.03	0.185	0.066	0.057	0.313	7.983	0.005
		GA	0.70±1.05	0.122	0.045	0.035	0.209	7.500	0.006
		AA	0.62±1.07	0^a
	rs167771	GG	0.62±1.07	-0.177	0.051	-0.276	-0.078	12.207	0.000
		GA	0.69±1.06	-0.070	0.069	-0.204	0.064	1.037	0.309
		AA	0.74±1.04	0^a
P_f	rs226082	CC	17.62±1.04	0.008	0.012	-0.014	0.031	0.532	0.466
		CT	18.26±1.04	0.024	0.010	0.004	0.044	5.681	0.017
		TT	17.28±1.03	0^a
	rs167771	GG	17.28±1.04	0.011	0.011	-0.010	0.032	1.111	0.292
		GA	19.10±1.06	0.055	0.021	0.014	0.096	6.825	0.009
		AA	16.84±1.03	0^a
m_l	rs2134655	GG	22.17±1.03	-0.120	0.056	-0.229	-0.012	4.712	0.026
		GA	23.80±1.04	-0.052	0.044	-0.138	0.035	1.372	0.236
		AA	25.03±1.06	0^a
	rs226082	CC	23.07±1.05	-0.007	0.038	-0.081	0.067	0.036	0.811
		CT	24.58±1.04	0.055	0.022	0.013	0.097	6.505	0.013
		TT	23.28±1.04	0^a
	rs167771	GG	22.87±1.06	0.012	0.042	-0.071	0.094	0.078	0.831
		GA	25.47±1.05	0.115	0.045	0.028	0.202	6.644	0.008
		AA	22.66±1.04