Polymorphism of methylenetetrahydrofolate reductase gene and chromosomal abnormalities among childbearing age women of different nationalities in Xinjiang Uygur Autonomous Region

doi:10.3877/cma.j.issn.1673-5250.2022.05.015

Objective

To investigate correlation between embryonic abortion(EA) and methylenetetrahydrofolate reductase (MTHFR) gene and methionine synthase reductase (MTRR) gene polymorphisms and chromosomal abnormalities in women of childbearing age in Xinjiang.

Methods

From May 2017 to January 2020, a total of 200 women of childbearing age who were treated at the Eighth People′s Hospital of Xinjiang Uygur Autonomous Region for EA were selected into this study. According to different nationalities, they were divided into Han group (n=100) and Uygur group (n=100). The MTHFR gene C677T, MTHFR gene A1298C and MTRR gene A66G were detected by real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) technology, and genotyping and chromosome abnormality were analyzed. The study met requirements of Helsinki Declaration of World Medical Association newly revised in 2013. Informed consent was obtained from each participate.

Results

①In the Han group, the percentage of CC and CT genotypes at the C677T locus of MTHFR gene (18.0%, 36.0%) and the percentage of AA genotypes at the A66G locus of MTRR gene (38.0%) were lower than those in the Uygur group (38.0%, 56.0%, 65.0%), and the differences were statistically significant when compared between two groups (χ²=9.92, 8.05, 14.59; P<0.05). And in the Han group, the percentage of TT genotype at the C677T locus of the MTHFR gene (46.0%) and the percentage of AG and GG genotypes at the A66G locus of the MTRR gene (40.0%, 22.0%) were higher than those in the Uygur group (6.0%, 33.0%, 2.0%), and the differences were also statistically significant when compared between groups (χ²=41.58, 14.59, 6.71, P<0.05). ②The proportions of C allele at the C677T locus of MTHFR gene (35.0%) and A allele at the A66G locus of MTRR gene (68.0%) in the Han group were lower than those in the Uygur group (66.0% and 82.0%), and the difference were statistically significant (P<0.05) when comparing between two groups; the proportions of T allele at the C677T locus of MTHFR gene and the G allele at the A66G locus of MTRR gene in the Han group were higher than those in the Uygur group, and the differences were also statistically significant (P<0.05) when comparing between two groups. The distribution of G alleles at the C677T locus of the MTHFR gene and the A66G locus of the MTRR gene in the Han group were higher than those in the Uygur group, and the differences were statistically significant (P<0.05) when comparing between two groups. ③The incidence of chromosomal abnormalities in 200 patients was 27.5% (45/200). Spearman rank correlation analysis showed a positive correlation between the incidence of chromosomal abnormalities and the expression of MTHFR gene C677T and MTRR gene A66G in patients with EA (r_s=0.625, P=0.031; r_s=0.784, P=0.022).

Conclusions

The polymorphism of MTHFR gene in women of childbearing age in Xinjiang is widely distributed, and there is a certain correlation with chromosome abnormality.

Key words: Embryo abortion, Methylenetetrahydrofolate reductase, Methionine synthase reductase, Gene frequency, Alleles, Chromosome aberrations, Xinjiang region, Women

表1 　MTHFR基因C677T、A1298C位点和MTRR基因A66G位点的引物序列

引物类型	引物序列	长度(bp)
β-actin	正向引物：5′-GCTGAGTCCTCTTGCTGTGCTC-3′	91
	反向引物：5′-GTACCTGGAGGCTTGGCATGAC-3′
MTHFR基因C677T位点	正向引物：5′- GGAGCGAGATCCCTCCAAAAT-3′	73
	反向引物：5′-GGCTGTTGTCATACTTCTCATGG-3′
MTHFR基因A1298C位点	正向引物：5′-CAGGATGCAGCAGGTGGAAGC-3′	84
	反向引物：5′-TGCTCCAGGCTGTAGTCTGTGG-3′
MTRR基因A66G位点	正向引物：5′-AGGTTCCTCAGCAGATCATTCTC-3′	69
	反向引物：5′-GAGCGGCATTCTGAGGTCTTAC-3′

表1 　MTHFR基因C677T、A1298C位点和MTRR基因A66G位点的引物序列

引物类型	引物序列	长度(bp)
β-actin	正向引物：5′-GCTGAGTCCTCTTGCTGTGCTC-3′	91
	反向引物：5′-GTACCTGGAGGCTTGGCATGAC-3′
MTHFR基因C677T位点	正向引物：5′- GGAGCGAGATCCCTCCAAAAT-3′	73
	反向引物：5′-GGCTGTTGTCATACTTCTCATGG-3′
MTHFR基因A1298C位点	正向引物：5′-CAGGATGCAGCAGGTGGAAGC-3′	84
	反向引物：5′-TGCTCCAGGCTGTAGTCTGTGG-3′
MTRR基因A66G位点	正向引物：5′-AGGTTCCTCAGCAGATCATTCTC-3′	69
	反向引物：5′-GAGCGGCATTCTGAGGTCTTAC-3′

表2 2组EA患者一般临床资料比较

组别	例数	年龄(岁，±s)	体重(kg，±s)	既往病史[例数(%)]
组别	例数	年龄(岁，±s)	体重(kg，±s)	2型糖尿病	原发性高血压疾病	高脂血症
汉族组	100	33.5±4.4	71.4±5.3	3(3.0)	2(2.0)	5(5.0)
维吾尔族组	100	33.8±4.8	71.8±5.5	4(4.0)	5(5.0)	7(7.0)
统计量		t＝0.46	t＝0.52	χ²<0.01^a	χ²＝0.59	χ²＝0.09
P值		0.646	0.601	>0.999	0.663	0.766

表2 2组EA患者一般临床资料比较

组别	例数	年龄(岁，±s)	体重(kg，±s)	既往病史[例数(%)]
组别	例数	年龄(岁，±s)	体重(kg，±s)	2型糖尿病	原发性高血压疾病	高脂血症
汉族组	100	33.5±4.4	71.4±5.3	3(3.0)	2(2.0)	5(5.0)
维吾尔族组	100	33.8±4.8	71.8±5.5	4(4.0)	5(5.0)	7(7.0)
统计量		t＝0.46	t＝0.52	χ²<0.01^a	χ²＝0.59	χ²＝0.09
P值		0.646	0.601	>0.999	0.663	0.766

表3 2组EA患者MTHFR、MTRR基因型分布比较[例数(%)]

组别	例数	MTHFR基因C677T位点			MTHFR基因A1298C位点			MTRR基因A66G位点
组别	例数	CC	TT	CT	AA	AG	GG	AA	AG	GG
汉族组	100	18(18.0)	46(46.0)	36(36.0)	75(75.0)	20(20.0)	5(5.0)	38(38.0)	40(40.0)	22(22.0)
维吾尔族组	100	38(38.0)	6(6.0)	56(56.0)	76(86.0)	21(21.0)	3(3.0)	65(65.0)	33(33.0)	2(2.0)
χ²值		9.92	41.58	8.05	0.03	0.03	0.52	14.59	0.19	6.71
P值		0.001	<0.001	0.005	0.869	0.861	0.470	<0.001	0.663	0.025

表3 2组EA患者MTHFR、MTRR基因型分布比较[例数(%)]

组别	例数	MTHFR基因C677T位点			MTHFR基因A1298C位点			MTRR基因A66G位点
组别	例数	CC	TT	CT	AA	AG	GG	AA	AG	GG
汉族组	100	18(18.0)	46(46.0)	36(36.0)	75(75.0)	20(20.0)	5(5.0)	38(38.0)	40(40.0)	22(22.0)
维吾尔族组	100	38(38.0)	6(6.0)	56(56.0)	76(86.0)	21(21.0)	3(3.0)	65(65.0)	33(33.0)	2(2.0)
χ²值		9.92	41.58	8.05	0.03	0.03	0.52	14.59	0.19	6.71
P值		0.001	<0.001	0.005	0.869	0.861	0.470	<0.001	0.663	0.025

表4 2组不同风险等级EA患者的年龄分布[例数(%)]

组别		25~29岁	30~35岁	36~40岁	41~46岁	>46岁	合计
维吾尔族组
	无风险	0(0)	7(36.8)	8(42.1)	4(21.0)	0(0)	19(19.0)
	低风险	3(5.9)	15(29.4)	19(37.2)	11(21.6)	3(5.9)	51(51.0)
	中风险	4(14.8)	6(22.2)	9(33.3)	6(22.2)	2(7.4)	27(27.0)
	高风险	0(0)	0(0)	0(0)	0(0)	1(1.0)	3(3.0)
	合计	7(7.0)	30(30.0)	36(36.0)	21(21.0)	6(6.0)	100(100.0)
汉族组
	无风险	3(25.0)	3(25.0)	5(41.7)	1(8.3)	0(0)	12(12.0)
	低风险	6(10.3)	24(41.4)	15(25.9)	10(17.2)	3(5.2)	58(58.0)
	中风险	5(20.0)	9(36.0)	9(36.0)	1(4.0)	1(4.0)	25(25.0)
	高风险	3(60.0)	1(20.0)	1(20.0)	0(0)	0(0)	5(5.0)
	合计	17(17.0)	37(37.0)	30(30.0)	12(12.0)	4(4.0)	100(100.0)

表4 2组不同风险等级EA患者的年龄分布[例数(%)]

组别		25~29岁	30~35岁	36~40岁	41~46岁	>46岁	合计
维吾尔族组
	无风险	0(0)	7(36.8)	8(42.1)	4(21.0)	0(0)	19(19.0)
	低风险	3(5.9)	15(29.4)	19(37.2)	11(21.6)	3(5.9)	51(51.0)
	中风险	4(14.8)	6(22.2)	9(33.3)	6(22.2)	2(7.4)	27(27.0)
	高风险	0(0)	0(0)	0(0)	0(0)	1(1.0)	3(3.0)
	合计	7(7.0)	30(30.0)	36(36.0)	21(21.0)	6(6.0)	100(100.0)
汉族组
	无风险	3(25.0)	3(25.0)	5(41.7)	1(8.3)	0(0)	12(12.0)
	低风险	6(10.3)	24(41.4)	15(25.9)	10(17.2)	3(5.2)	58(58.0)
	中风险	5(20.0)	9(36.0)	9(36.0)	1(4.0)	1(4.0)	25(25.0)
	高风险	3(60.0)	1(20.0)	1(20.0)	0(0)	0(0)	5(5.0)
	合计	17(17.0)	37(37.0)	30(30.0)	12(12.0)	4(4.0)	100(100.0)

表5 2组EA患者MTHFR、MTRR基因型等位基因分布频率比较[例数(%)]

组别	例数	MTHFR基因C677T位点		MTHFR基因A1298C位点		MTRR基因A66G位点
组别	例数	C	T	A	G	A	G
汉族组	100	35(35.0)	65(65.0)	88(88.0)	12(12.0)	68(68.0)	32(32.0)
维吾尔族组	100	66(66.0)	34(34.0)	87(87.0)	13(13.0)	82(82.0)	18(18.0)
χ²值		19.22		0.05		5.23
P值		<0.005		0.830		0.022

表5 2组EA患者MTHFR、MTRR基因型等位基因分布频率比较[例数(%)]

组别	例数	MTHFR基因C677T位点		MTHFR基因A1298C位点		MTRR基因A66G位点
组别	例数	C	T	A	G	A	G
汉族组	100	35(35.0)	65(65.0)	88(88.0)	12(12.0)	68(68.0)	32(32.0)
维吾尔族组	100	66(66.0)	34(34.0)	87(87.0)	13(13.0)	82(82.0)	18(18.0)
χ²值		19.22		0.05		5.23
P值		<0.005		0.830		0.022

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