亚甲基四氢叶酸还原酶基因C677T多态性与中国2型糖尿病患者冠心病风险增加相关

doi:10.24920/003792

摘要/Abstract

摘要：

目的长期血糖控制不佳引起的慢性心血管疾病是2型糖尿病患者主要的死亡原因。研究表明：亚甲基四氢叶酸还原酶基因（methylenetetrahydrofolate reductase gene,MTHFR）多态性可能会影响2型糖尿病患者冠心病的发生。本研究旨在评估MTHFR C677T和A1298C基因突变是否与2型糖尿病患者冠心病的发生风险相关。
方法本研究一共纳入197例2型糖尿病受试者,其中95例受试者合并冠心病。采用双脱氧链终止法对MTHFR C677T和A1298C进行基因分型,并分析比较合并冠心病与不合并冠心病受试者等位基因频率的差异。
结果合并冠心病2型糖尿病受试者的677T等位基因频率明显高于不合并冠心病的受试者（P=0.011）。单倍型频率在合并冠心病与不合并冠心病的2型糖尿病受试者之间无显著的差异。在同型半胱氨酸水平较低的糖尿病受试者中（≤15μmol/L）,携带677T等位基因的受试者发生冠心病风险更高（P=0.006）,而在同型半胱氨酸水平较高的糖尿病受试者中（>15μmol/L）,MTHFR基因多态性对冠心病的发生风险无影响（P=0.491）。
结论 MTHFRC677T基因多态性与糖尿病患者发生冠心病的风险相关,对于具有正常同型半胱氨酸水平的中国糖尿病人群,其可作为预测冠心病风险的有效标志物。

关键词: 亚甲基四氢叶酸还原酶, 基因多态性, 2型糖尿病, 冠心病, 同型半胱氨酸

Abstract:

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus (T2DM). Previous researches report that methylenetetrahydrofolate reductase gene (MTHFR) polymorphisms might influence the occurrence of coronary heart disease (CHD) in T2DM patients. The purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD in T2DM patients.
Methods A total of 197 subjects with T2DM were studied, of which 95 patients with CHD. The genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method, and compared between patients with CHD and those without CHD.
Results We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD (P=0.011). However, there was no significant difference in any of the examined haplotypes between T2DM patients with and without CHD. Furthermore, the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (P=0.006), while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hcy levels (>15 μmol/L) (P=0.491).
Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hcy levels.

Key words: methylenetetrahydrofolate reductase, gene polymorphism, type 2 diabetes mellitus, coronary heart diseases, homocysteine

Kunrong Wu, Shufang Zhang, Ziwan Guan, Xiaoli Li, Rui Li, Ying Yin, Yan Li. Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients[J].Chinese Medical Sciences Journal, 2021, 36(2): 103-109.

图/表 6

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Items	T2DM patients without CHD	T2DM patients with CHD	Pvalue
n	102	95
Male [n (%)]	67 (65.69)	62 (65.26)	0.950
Age (yrs)	63.14±6.78	64.34±8.11	0.263
Current smoker [n (%)]	26 (25.49)	27 (28.42)	0.547
Age at T2DM diagnosis (yrs)	50.23±7.93	51.67±9.80	0.257
Diabetes duration (yrs)	12.91±5.97	12.66±6.66	0.642
BMI (kg/m²)	25.07±2.99	25.18±2.79	0.787
FPG (mmol/L)	7.95±2.08	8.10±2.33	0.733
HbA1c (%)	8.57±1.67	8.33±2.17	0.115
TC (mmol/L)	4.59±1.02	4.44±1.05	0.337
TG (mmol/L)	1.60±0.96	1.42±0.67	0.553
HDL-C (mmol/L)	1.21±0.28	1.20±0.39	0.523
LDL-C (mmol/L)	2.64±0.83	2.52±0.75	0.436
SBP (mm Hg)	133.26±12.42	131.01±13.62	0.228
DBP (mm Hg)	75.85±7.34	74.89±9.17	0.420
Scr (μmol/L)	66.21±18.40	70.25±22.48	0.128

Genotypes and alleles	T2DM patients [n (%)]		OR(95%CI)	P value
Genotypes and alleles	Without CHD (n=102)	With CHD (n=95)	OR(95%CI)	P value
CC	22 (21.57)	9 (9.47)
CT+TT	80 (78.43)	86 (90.53)	2.63 (1.14-6.05)	0.020
C allele	92 (45.10)	62 (32.63)
T allele	112 (54.90)	128 (67.37)	1.70 (1.13-2.56)	0.011

Genotypes and alleles	T2DM patients [n (%)]		OR (95%CI)	P value
Genotypes and alleles	Without CHD (n=100)	With CHD (n=67)	OR (95%CI)	P value
AA	64 (69.07)	48 (74.60)
AC+CC	36 (30.93)	19 (25.40)	0.70 (0.36-1.38)	0.303
A allele	162 (83.51)	115 (87.30)
C allele	38 (16.49)	19 (12.70)	0.70 (0.39-1.28)	0.251

Haplotypes*	Frequency		OR (95%CI)	P value
Haplotypes*	T2DM without CHD (n=67)	T2DM with CHD (n=67)	OR (95%CI)	P value
C-A	0.267	0.216	0.75 (0.45-1.26)	0.275
C-C	0.183	0.142	0.73 (0.40-1.34)	0.310
T-A	0.543	0.642	1.49 (0.95-2.33)	0.084

Hcy levels (μmol/L)	MTHFR genotypes	Patients without CHD (n)	Patients with CHD (n)	OR(95%CI)	P value
5-15.0	677CC	21	4
	677CT+TT	67	56	4.39 (1.42-13.54)	0.006
	1298AA	55	31
	1298AC+CC	31	10	0.57 (0.25-1.32)	0.189
>15.0	677CC	1	5
	677CT+TT	13	30	0.46 (0.05-4.35)	0.491
	1298AA	9	17
	1298AC+CC	5	9	0.95 (0.25-3.71)	0.945

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