糖代谢及脂肪调控基因多态性与儿童肥胖代谢异常的关联

夏志伟; 宫照龙; 刘婷婷; 王路; 赵海; 孙冰洁; 李岩; 殷继永; 霍军生

doi:10.16835/j.cnki.1000-9817.2025172

糖代谢及脂肪调控基因多态性与儿童肥胖代谢异常的关联

doi: 10.16835/j.cnki.1000-9817.2025172

夏志伟^{1, 2},
宫照龙¹,
刘婷婷¹,
王路²,
赵海²,
孙冰洁²,
李岩¹,
殷继永¹,
霍军生^1, ,

1.
中国疾病预防控制中心营养与健康所/国家卫生健康委公共营养与健康重点实验室，北京 100050
2.
北京市疾病预防控制中心学校卫生所

基金项目:

国家财政项目“公共卫生应急-营养健康与合理膳食行动” 102393220020070000012

详细信息

作者简介:
夏志伟(1989-)，男，安徽铜陵人，在读博士，主管医师，主要研究方向为学校卫生

通讯作者:
霍军生，E-mail: huojs@ninh.chinacdc.cn

利益冲突声明 所有作者声明无利益冲突。
中图分类号: R179 R723.14 Q344^+.13
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- 被引次数: 0
出版历程
- 收稿日期: 2025-05-07
- 修回日期: 2025-05-21
- 网络出版日期: 2025-07-04
- 刊出日期: 2025-06-25

Association between polymorphisms in the glucose metabolism and lipid regulation genes with metabolic abnormalities in childhood obesity

1.
Institute of Nutrition and Health, Chinese Center for Disease Control and Prevention/NHC Key Laboratory of Public Nutrition and Health, Beijing(100050), China

摘要

摘要: 目的探讨CDKAL1基因rs35261542、FAIM2基因rs3205718及VGLL4基因rs2574704多态性位点与儿童肥胖及合并代谢表型的关联性，为制定儿童肥胖个性化防控措施提供依据。方法基于2023年“早期儿童营养包干预长期营养健康作用评估”项目，选取河南(嵩县、汝阳县)、贵州(贵定县、福泉县)4县1 078名5~7岁儿童，按体质量指数Z评分(BMI Z评分)筛选出超重肥胖(OVOB)组儿童87名，按性别、年龄和BMI Z评分匹配体重正常组儿童117名；并按4项传统心脏代谢危险因素(CRs)标准，分为代谢正常体重正常(MHWH，51人)、代谢异常体重正常(MUWH，66人)、代谢正常型肥胖(MHO，31人)和代谢异常型肥胖(MUO，56人)4组。通过问卷调查、体格测量、血清生化检测及KASP基因分型技术，分析基因多态性在不同代谢异质性儿童中的分布，采用多因素Logistic回归模型评估3个基因多态性位点与儿童肥胖及合并代谢表型的关联性。结果多因素Logistic回归分析结果显示，CDKAL1 rs35261542纯合突变型AA与OVOB、MHO和MUO的发生风险均呈正相关(OR值分别为3.63，11.04，4.88，P值均 < 0.05)；FAIM2 rs3205718纯合突变型TT与OVOB发生风险呈正相关(OR=4.44，P < 0.05)，但与代谢表型关联无统计学意义(P值均>0.05)；VGLL4 rs2574704纯合突变型TT降低MHO和MUO发生风险(OR值分别为0.30，0.24，P值均 < 0.05)。基因型累积效应分析显示，rs35261542+rs3205718组合携带1个和2个风险基因型者OVOB发生风险增加(OR值分别为2.53，20.79)；rs35261542+rs2574704组合MHO和MUO发生风险均增加(OR值分别为8.50，5.00)(P值均 < 0.05)。结论 rs35261542位点AA型与儿童肥胖及合并代谢异常呈正相关，rs3205718位点TT型与儿童肥胖呈正相关，rs2574704位点TT型与代谢表型呈负相关，且多态性位点风险基因型的数量具有累积效应。
- 儿童 /
- 肥胖症 /
- 基因 /
- 代谢疾病 /
- 回归分析
Abstract: Objective To explore the association between CDKAL1 rs35261542, FAIM2 rs3205718, and VGLL4 rs2574704 polymorphisms with childhood obesity and related metabolic phenotypes to provide evidence for personalized prevention and management strategies. Methods Based on the 2023 Long-term Nutritional Health Effects of Early Childhood Nutrition Package Intervention project, the study enrolled 1 078 children aged 5-7 years from four counties in Henan (Songxian and Ruyang countries) and Guizhou (Guiding and Fuquan countries) provinces. Using BMI Z-scores, 87 overweight and obese(OVOB) children were selected and matched by sex, age, and BMI Z-score with 117 normal-weight controls. Participants were further stratified into four metabolic phenotype groups: metabolically healthy normal weight (MHNW, n=51), metabolically unhealthy normal weight (MUNW, n=66), metabolically healthy obesity (MHO, n=31) and metabolically unhealthy obesity (MUO, n=56) based on four conventional cardiometabolic risk factor (CR) criteria. Data were collected through questionnaires, anthropometric measurements, serum biochemical tests, and KASP genotyping. The distribution of three genetic polymorphisms (CDKAL1 rs35261542, FAIM2 rs3205718, VGLL4 rs2574704) across metabolic subgroups was analyzed. Multivariate Logistic regression models assessed associations between these polymorphisms and obesity/metabolic phenotypes. Results Multivariate Logistic regression analysis showed that Homozygous mutant AA genotype of CDKAL1 rs35261542 was positively associated with OVOB(OR=3.63), MHO (OR=11.04), MUO (OR=4.88) (P < 0.05). Homozygous TT genotype of FAIM2 rs3205718 increased OVOB risk (OR=4.44, P < 0.05) but showed no association with metabolic phenotypes (P>0.05). Homozygous mutant TT of VGLL4 rs2574704 reduced the risks of MHO and MUO (OR=0.30, 0.24, P < 0.05). Cumulative genetic effects analysis demonstrated carriers of 1 or 2 risk genotypes of rs35261542 and rs3205718 had progressively higher OVOB risk (OR=2.53, 20.79), and the combination of rs35261542 and rs2574704 increased risks for both MHO (OR=8.50) and MUO (OR=5.00) (P < 0.05). Conclusions The AA genotype of rs35261542 (CDKAL1) positively correlates with childhood obesity and metabolic abnormalities. The TT genotype of rs3205718 (FAIM2) increases obesity risk but not metabolic phenotypes. The TT genotype of rs2574704 (VGLL4) shows protective effects against metabolic dysfunction. Risk genotypes exhibit dose-dependent cumulative effects on obesity and metabolic outcomes.
- Child /
- Obesity /
- Genes /
- Metabolic diseases /
- Regression analysis
注释:

1) 利益冲突声明 所有作者声明无利益冲突。

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表 1 不同组别儿童生化指标比较(x±s)

Table 1. Comparison of biochemical indicators in children of different groups(x±s)

组别	代谢类型	人数	TCHO/ (mmol·L^-1)	TG/ (mmol·L^-1)	HDL-C/ (mmol·L^-1)	LDL-C/ (mmol·L^-1)	FBG/ (mmol·L^-1)	ADP/ (μg·mL^-1)	ALT/ (U·IL^-1)	AST/ (U·L^-1)	CRP-H/ (mg·L^-1)
NOR	MHWH	51	4.26±0.68	0.97±0.30	1.65±0.28	1.64±0.39	5.06±0.82	16.06±5.35	10.18±3.73	27.85±5.84	0.75±1.27
	MUWH	66	4.22±0.80	1.10±0.47	1.51±0.57	1.51±0.54	5.58±1.72	13.93±5.70	10.19±3.59	26.67±4.80	0.92±1.85
	小计	117	4.24±0.75	1.04±0.41	1.57±0.47	1.57±0.48	5.35±1.42	14.86±5.63	10.19±3.63	27.19±5.29	0.84±1.62
OVOB	MHO	31	4.43±0.47	1.04±0.34	1.62±0.27	1.80±0.37	4.99±0.99	12.46±5.49	11.71±4.59	26.26±4.97	3.15±7.28
	MUO	56	4.33±0.68	1.75±1.19	1.45±0.40	1.67±0.51	5.71±1.28	14.14±6.64	14.13±11.66	29.61±13.52	1.78±2.99
	小计	87	4.36±0.61	1.50±1.03	1.51±0.37	1.71±0.47	5.45±1.23	13.54±6.28	13.27±9.78	28.41±11.32	2.27±4.97
合计		204	4.29±0.69	1.24±0.77	1.54±0.43	1.63±0.48	5.39±1.34	14.30±5.94	11.51±7.11	27.72±8.42	1.45±3.53
F值			0.71	13.90	2.53	2.96	3.62	2.97	4.07	1.60	3.88
P值			0.55	< 0.01	0.06	0.03	0.01	0.03	0.01	0.19	0.01
注： F值为4组代谢类型间比较。

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表 2 不同体重合并代谢表型儿童rs35261542、rs3205718和rs2574704位点分布特征

Table 2. Distribution characteristics of rs35261542, rs3205718 and rs2574704 loci in different weights children with metabolic heterogeneity

单核苷酸多态性基因	基因型	NOR			OVOB			合计(n=204)
单核苷酸多态性基因	基因型	MHWH(n=51)	MUWH(n=66)	小计(n=117)	MHO(n=31)	MUO(n=56)	小计(n=87)	合计(n=204)
rs35261542	AA	4(7.8)	7(10.6)	11(9.4)	7(22.6)	14(25.0)	21(24.1)	32(15.7)
	CA	23(45.1)	39(59.1)	62(53.0)	18(58.1)	22(39.3)	40(46.0)	102(50.0)
	CC	24(47.1)	20(30.3)	44(37.6)	6(19.4)	20(35.7)	26(29.9)	70(34.3)
rs3205718	CC	33(64.7)	35(53.0)	68(58.1)	14(45.2)	32(57.1)	46(52.9)	114(55.9)
	CT	16(31.4)	29(43.9)	45(38.5)	12(38.7)	16(28.6)	28(32.2)	73(35.8)
	TT	2(3.9)	2(3.0)	4(3.4)	5(16.1)	8(14.3)	13(14.9)	17(8.3)
rs2574704	CC	9(17.6)	29(43.9)	38(32.5)	14(45.2)	20(35.7)	34(39.1)	72(35.3)
	CT	36(70.6)	31(41.0)	67(57.3)	14(45.2)	26(46.4)	40(46.0)	107(52.5)
	TT	6(11.8)	6(9.1)	12(10.3)	3(9.7)	10(17.9)	13(14.9)	25(12.3)
注： ()内数字为构成比/%。

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表 3 基因多态性位点rs35261542、rs3205718和rs2574704与肥胖儿童合并代谢表型关联性分析(n=204)

Table 3. Association analysis of gene polymorphism loci rs35261542, rs3205718 and rs2574704 with metabolic heterogeneity in obese children(n=204)

自变量	基因型	OVOB		MHO		MUO
自变量	基因型	OR值(95%CI)	P值	OR值(95%CI)	P值	OR值(95%CI)	P值
rs35261542	AA	3.63(1.34~9.84)	0.01	11.04(2.07~58.91)	0.01	4.88(1.23~19.37)	0.02
	CA	1.23(0.59~2.54)	0.58	4.66(1.35~16.16)	0.02	1.33(0.51~3.44)	0.56
	CC	1.00		1.00		1.00
显性模型	AA	3.19(1.32~7.73)	0.01	4.01(0.98~16.40)	0.05	4.11(1.15~14.71)	0.03
	CA+CC	1.00		1.00		1.00
隐性模型	AA+CA	0.63(0.32~1.26)	0.19	5.57(1.68~18.53)	0.01	1.86(0.76~4.52)	0.17
	CC	1.00		1.00		1.00
rs3205718	TT	4.44(1.23~16.06)	0.02	5.35(0.82~34.92)	0.08	3.44(0.59~20.11)	0.17
	CT	0.97(0.49~1.91)	0.92	1.92(0.67~5.49)	0.23	1.13(0.45~2.83)	0.80
	CC	1.00		1.00		1.00
隐性模型	CC+CT	1.00		1.00		1.00
	TT	4.50(1.28~15.87)	0.02	4.14(0.67~25.61)	0.13	3.30(0.58~18.69)	0.18
rs2574704	CC	1.00		1.00		1.00
	TC	0.71(0.24~2.10)	0.54	0.33(0.06~1.97)	0.22	0.47(0.11~2.06)	0.32
	TT	0.57(0.29~1.15)	0.12	0.30(0.10~0.94)	0.04	0.24(0.09~0.67)	0.01
显性模型	CC	1.00		1.00		1.00
	TC+TT	1.69(0.86~3.32)	0.13	0.30(0.10~0.91)	0.03	0.27(0.10~0.73)	0.01
注：校正性别、年龄、出生体重、是否母乳喂养、母乳喂养时间和CRP-H、ALT、ADP等协变量；因变量体重分组以NOR为参照，代谢异常表型分组以MHWH为参照。

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