CYP19，COMT等位基因突变与子宫内膜异位症和子宫腺肌病的相关性研究

doi:10.3877/cma.j.issn.1673-5250.2013.01.014

目的

探讨山东省滨州地区汉族妇女CYP19基因240A/G，COMT基因1947G/A位点单核苷酸多态性(SNP)与子宫内膜异位症(EMs)和子宫腺肌病(AM)发病的关系。

方法

收集2011年9月至2012年3月于本院妇产科行盆、腹腔手术，并经术后组织病理学检查证实为EMs和AM者80例为研究对象，并将其分别纳入EMs组(n＝30)和AM组(n＝50)，选取同期于本院行盆、腹腔手术并经肉眼及术后组织病理学检查排除EMs和AM者38例纳入对照组。采集其晨空腹外周静脉血(3～4)mL，采用聚合酶链反应－限制性片段长度多态性(PCR－RFLP)技术检测2者基因多态性与EMs和AM发病的关系(本研究遵循的程序符合本院人体试验委员会制定的伦理学标准，得到该委员会批准，分组征得受试对象的知情同意)。

结果

CYP19 240A/G位点各基因型及等位基因分布频率在EMs组，AM组和对照组比较，差异均有统计学意义(P<0.05)，其中等位基因G突变可使EMs发病风险增加2.463倍，AM发病风险增加2.705倍，携带AG和GG基因型妇女的EMs发病风险增加4.444倍，AM发病风险增加3.939倍。COMT 1947G/A位点各基因型及等位基因分布频率在EMs组，AM组和对照组比较，差异无统计学意义(P>0.05)，携带A等位基因突变的基因型GA＋AA分别与野生型GG比较，差异无统计学意义(P>0.05)，携带A等位基因的基因型(GA＋AA)不能增加EMs和AM发病风险。

结论

滨州地区汉族妇女CYP19基因240A/G等位基因突变，可增加EMs和AM发病风险，而COMT基因1947G/A等位基因突变与EMs和AM发病风险无相关性。

关键词: 子宫内膜异位症, 子宫腺肌病, CYP19, COMT, 等位基因突变

Objective

To investigate the correlation of polymorphism of CYP19 240A/G, COMT 1947G/A, endometriosis (EMs) and adenomyosis (AM).

Methods

From September 2011 to March 2012, thirty cases of EMs and 50 cases of AM were recruited into this study. Meanwhile, thirty-eight cases without EMs and AM were included into control group. The blood were collected from all of them in the morning after the operation. The correlation between the multibus of two genes about EMs and AM was evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Affiliated Hospital of Binzhou Medical College. Informed consent was obtained from all participates.

Results

There were a significant difference of the alleles and genotype of CYP19 240A/G between EMs group, AM group and control group (P<0.05). The mutant allele of G made relative risk suffered from EMs and AM got 2.463 times, 2.705 times, respectively. The relative risks suffered from EMs and AM of AG and GG genotype were 4.444 and 3.939 times of GG genotype, respectively. There were no significant difference of the alleles and genotype of COMT 1947G/A between EMs group, AM group and control group (P>0.05). There were no significance between the genotype that caught A(GA+ AA)and GG genotype (P>0.05). There was no correlation between GA and AA genotype and the risk suffered from EMs and AM.

Conclusions

The mutant allele of CYP19 240A/G increased the risk suffered from EMs and AM. The mutant allele of COMT 1947A/G had no relationship with the risk of EMs and AM.

Key words: endometriosis, adenomyosis, CYP19, COMT, mutant allele

表1 CYP19基因240A/G和COMT基因1947G/A引物序列、褪火温度、扩增片段长度

Table 1 The primer sequence, annealing temperature and amplified fragment length of CYP19 240A/G and COMT 1947G/A, respectively

基因	引物序列(5'→3')	褪火温度(℃)	扩增片段长度(bp)
CYP19 240A/G	AGTAACACAGAACAGTTGCA	51	188
?	TCCAGACTCGCATGAATTCTCCGTA	?	?
COMT 1947G/A	TCGTGGACGCCGTGATTCAGG	59	217
?	AGGTCTGACAACGGGTCAGGC	?	?

表1 CYP19基因240A/G和COMT基因1947G/A引物序列、褪火温度、扩增片段长度

Table 1 The primer sequence, annealing temperature and amplified fragment length of CYP19 240A/G and COMT 1947G/A, respectively

基因	引物序列(5'→3')	褪火温度(℃)	扩增片段长度(bp)
CYP19 240A/G	AGTAACACAGAACAGTTGCA	51	188
?	TCCAGACTCGCATGAATTCTCCGTA	?	?
COMT 1947G/A	TCGTGGACGCCGTGATTCAGG	59	217
?	AGGTCTGACAACGGGTCAGGC	?	?

图1 CYP19 240A/G位点各基因型(M: marker；1: AG；2: AA；3: GG)

Figure 1 Each genotype of CYP19 240A/G(M: marker，1: AG；2: AA；3: GG)

图2 COMT 1947G/A位点各基因型(M: marker；1: AA；2: GG；3: GA)

Figure 2 Each genotype of COMT 1947G/A(M: marker；1: AA；2: GG；3: GA)

表2 CYP19，COMT各基因型在EMs组，AM组及对照组中的分布频率[n(%)]

Table 2 Frequency distribution of CYP19，COMT genotypes between EMs group, AM group and control group [n(%)]

组别		n	基因型频率			χ²	P
组别		n	AA	AG	GG	χ²	P
CYP19		?	?	?	?	?	?
?	EMs组	30	6(20.00)	17(56.67)	7(23.33)	7.569^a	0.023^a
?	AM组	50	11(22.00)	24(48.00)	15(30.00)	9.422^a	0.009^a
?	对照组	38	20(52.63)	13(34.21)	5(13.16)	?	?
COMT		?	?	?	?	?	?
?	EMs组	30	3(10.00)	11(36.67)	16(53.33)	0.861^a	0.650^a
?	AM组	50	3 (6.00)	17(34.00)	30(60.00)	1.007^a	0.605^a
?	对照组	38	4(10.53)	10(26.32)	24(63.16)	?	?

表2 CYP19，COMT各基因型在EMs组，AM组及对照组中的分布频率[n(%)]

Table 2 Frequency distribution of CYP19，COMT genotypes between EMs group, AM group and control group [n(%)]

组别		n	基因型频率			χ²	P
组别		n	AA	AG	GG	χ²	P
CYP19		?	?	?	?	?	?
?	EMs组	30	6(20.00)	17(56.67)	7(23.33)	7.569^a	0.023^a
?	AM组	50	11(22.00)	24(48.00)	15(30.00)	9.422^a	0.009^a
?	对照组	38	20(52.63)	13(34.21)	5(13.16)	?	?
COMT		?	?	?	?	?	?
?	EMs组	30	3(10.00)	11(36.67)	16(53.33)	0.861^a	0.650^a
?	AM组	50	3 (6.00)	17(34.00)	30(60.00)	1.007^a	0.605^a
?	对照组	38	4(10.53)	10(26.32)	24(63.16)	?	?

表3 CYP19，COMT各等位基因在EMs组，AM组及对照组中的频率分布(%)

Table 3 Frequency distribution of CYP19，COMT alleles between EMs group, AM group and control group (%)

组别		等位基因频率		χ²	P	OR	95%CI
组别		A	G	χ²	P	OR	95%CI
CYP19		?	?	?	?	?	?
?	EMs组	29	31	6.416^a	0.011^a	2.463^a	1.218～4.981
?	AM组	46	54	9.887^a	0.002^a	2.705^a	1.444～5.068
?	对照组	53	23	?	?	?	?
COMT		?	?	?	?	?	?
?	EMs组	17	43	0.379^a	0.538^a	1.274^a	0.589～2.755
?	AM组	23	77	0.011^a	0.915^a	0.962^a	0.476～1.947
?	对照组	18	58	?	?	?	?

表3 CYP19，COMT各等位基因在EMs组，AM组及对照组中的频率分布(%)

Table 3 Frequency distribution of CYP19，COMT alleles between EMs group, AM group and control group (%)

组别		等位基因频率		χ²	P	OR	95%CI
组别		A	G	χ²	P	OR	95%CI
CYP19		?	?	?	?	?	?
?	EMs组	29	31	6.416^a	0.011^a	2.463^a	1.218～4.981
?	AM组	46	54	9.887^a	0.002^a	2.705^a	1.444～5.068
?	对照组	53	23	?	?	?	?
COMT		?	?	?	?	?	?
?	EMs组	17	43	0.379^a	0.538^a	1.274^a	0.589～2.755
?	AM组	23	77	0.011^a	0.915^a	0.962^a	0.476～1.947
?	对照组	18	58	?	?	?	?

表4 EMs组与对照组CYP19，COMT突变型和野生型比较[n(%)]

Table 4 Comparison of mutant and wild type in CYP19，COMT between EMs group and control group[n(%)]

组别	n	CYP19		COMT
组别	n	AG＋GG	AA	GA＋AA	GG
EMs组	30	24(80.00)	6(20.00)	14(46.67)	16(53.33)
对照组	38	18(47.37)	20(52.63)	14(36.84)	24(63.16)
χ²	?	7.559		0.668
P	?	0.006		0.414
OR	?	4.444		1.500
95%CI	?	1.482～13.326		0.566～3.973

表4 EMs组与对照组CYP19，COMT突变型和野生型比较[n(%)]

Table 4 Comparison of mutant and wild type in CYP19，COMT between EMs group and control group[n(%)]

组别	n	CYP19		COMT
组别	n	AG＋GG	AA	GA＋AA	GG
EMs组	30	24(80.00)	6(20.00)	14(46.67)	16(53.33)
对照组	38	18(47.37)	20(52.63)	14(36.84)	24(63.16)
χ²	?	7.559		0.668
P	?	0.006		0.414
OR	?	4.444		1.500
95%CI	?	1.482～13.326		0.566～3.973

表5 AM组与对照组CYP19，COMT突变型和野生型比较[n(%)]

Table 5 Comparison of mutant and wild type in CYP19，COMT between AM group and control group[n(%)]

组别	n	CYP19		COMT
组别	n	AG＋GG	AA	GA＋AA	GG
AM组	50	39(78.00)	11(22.00)	20(40.00)	30(60.00)
对照组	38	18(47.37)	20(52.63)	14(36.84)	24(63.16)
χ²	?	8.878		0.091
P	?	0.003		0.763
OR	?	3.939		1.143
95%CI	?	1.569～9.992		0.479～2.724

表5 AM组与对照组CYP19，COMT突变型和野生型比较[n(%)]

Table 5 Comparison of mutant and wild type in CYP19，COMT between AM group and control group[n(%)]

组别	n	CYP19		COMT
组别	n	AG＋GG	AA	GA＋AA	GG
AM组	50	39(78.00)	11(22.00)	20(40.00)	30(60.00)
对照组	38	18(47.37)	20(52.63)	14(36.84)	24(63.16)
χ²	?	8.878		0.091
P	?	0.003		0.763
OR	?	3.939		1.143
95%CI	?	1.569～9.992		0.479～2.724

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Correlative Study on Mutant allele of CYP19 240A/G, COMT 1947G/A, Endometriosis and Adenomyosis

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Correlative Study on Mutant allele of CYP19 240A/G, COMT 1947G/A, Endometriosis and Adenomyosis