王淑媛魯衍強(qiáng)馬少杰△ 黃京希楊凱云熊 敏周玉珍楊 琦
湘潭市漢族女性MTHFR和MTRR基因多態(tài)性分布及其與血漿Hcy水平的關(guān)系
王淑媛1魯衍強(qiáng)2馬少杰2△黃京希1楊凱云1熊 敏1周玉珍1楊 琦3
目的 分析湖南省湘潭市女性5,10-亞甲基四氫葉酸還原酶(MTHFR)C677T、A1298C及甲硫氨酸合成酶還原酶(MTRR)A66G位點(diǎn)基因多態(tài)性的分布特征,并分析其多態(tài)性與血漿同型半胱氨酸(Hcy)水平的關(guān)系。方法以湘潭市1 701例女性為研究對(duì)象,檢測(cè)其MTHFR C677T、A1298C和MTRR A66G位點(diǎn)基因多態(tài)性,并對(duì)其中110例孕期女性檢測(cè)其血漿Hcy水平。統(tǒng)計(jì)分析本地區(qū)基因多態(tài)性的分布特征,并與淄博、鄭州、煙臺(tái)、鎮(zhèn)江、松滋、惠州、瓊海等地區(qū)進(jìn)行比較;分析多態(tài)性與血漿Hcy水平的關(guān)系。結(jié)果湘潭市女性的MTHFR C677T位點(diǎn)TT純合突變基因型頻率為12.6%,高于惠州(10.9%)、瓊海(6.1%),低于淄博(43.6%)、鄭州(36.8%)、煙臺(tái)(32.2%)、鎮(zhèn)江(21.8%),差異均有統(tǒng)計(jì)學(xué)意義。與松滋相比差異無統(tǒng)計(jì)學(xué)意義。MTHFR A1298C位點(diǎn)CC純合突變基因型頻率為4.8%,低于瓊海(7.1%)、高于淄博(1.4%)、鄭州(2.4%)、煙臺(tái)(1.8%)、鎮(zhèn)江(3.5%)、松滋(2.6%),差異均有統(tǒng)計(jì)學(xué)意義。MTRR A66G位點(diǎn)GG純合突變基因型頻率為6.8%,高于淄博(4.8%),低于瓊海(9.3%),差異有統(tǒng)計(jì)學(xué)意義。血漿Hcy濃度與MTHFR C677T位點(diǎn)基因型多態(tài)性有關(guān),TT型人群Hcy濃度高于CT型人群和CC型人群(μmol/L: 8.52±2.01 vs 5.94±1.47 vs 5.71±0.18);血漿Hcy濃度與MTHFR A1298C位點(diǎn)基因型多態(tài)性有關(guān),CC型人群Hcy濃度高于AA型人群和AC型人群(μmol/L:9.83±2.26 vs 6.35±2.13 vs 5.55±1.75);血漿Hcy濃度與MTRR A66G位點(diǎn)基因型無關(guān)。結(jié)論湘潭市女性MTHFR和MTRR基因多態(tài)性頻率不同于其他地區(qū),具有地域特異性。MTHFR C677T、A1298C位點(diǎn)多態(tài)性與Hcy水平有關(guān)。
亞甲基四氫葉酸還原酶;甲硫氨酸合成酶還原酶;基因多態(tài)性;同型半胱氨酸
我國(guó)是出生缺陷高發(fā)國(guó)家,出生缺陷總發(fā)生率約5.6%[1]。葉酸攝入不足或者不能被人體有效利用是導(dǎo)致出生缺陷的主要原因[2]。研究表明,5,10-亞甲基四氫葉酸還原酶(methylenetetrahydrofolate reductase,MTHFR)和甲硫氨酸合成酶還原酶(methionine synthase reductase,MTRR)是葉酸轉(zhuǎn)運(yùn)和代謝的關(guān)鍵酶[3]。MTHFR基因C677T位點(diǎn)、A1298C位點(diǎn)與MTRR基因A66G位點(diǎn)的多態(tài)性會(huì)造成MTHFR 與MTRR的酶活性降低,造成葉酸代謝異常,使DNA低甲基化導(dǎo)致唐氏綜合征[4]。葉酸代謝障礙會(huì)使同型半胱氨酸(Hcy)水平升高,而高同型半胱氨酸(HHcy)與神經(jīng)管缺陷、唇腭裂、先天性心臟病等出生缺陷[5],以及復(fù)發(fā)性流產(chǎn)[6]、妊娠期高血壓等孕期疾病密切相關(guān)[7]。育齡婦女作為一個(gè)特殊的群體,體內(nèi)葉酸營(yíng)養(yǎng)素的水平對(duì)于胎兒的健康生長(zhǎng)發(fā)育和孕婦的身體健康都有極其重要的影響。本研究通過檢測(cè)湘潭市育齡女性體內(nèi)MTHFR和MTRR編碼基因的3個(gè)多態(tài)性位點(diǎn),預(yù)測(cè)受檢者的葉酸代謝能力,從而指導(dǎo)孕婦在孕前及孕期適量補(bǔ)充葉酸,維持正常Hcy水平,預(yù)防出生缺陷的發(fā)生。同時(shí)了解湘潭地區(qū)婦女葉酸代謝相關(guān)基因的分布特點(diǎn)與群體遺傳學(xué)特征,為本地區(qū)預(yù)防出生缺陷制定針對(duì)性的干預(yù)措施提供科學(xué)依據(jù)。
1.1 研究對(duì)象 選取湘潭市自2012年11月—2014年2月到我院進(jìn)行孕前與孕期檢查的無親緣關(guān)系女性1 701例,均為漢族,平均年齡(26.72±4.60)歲。
1.2 方法
1.2.1 基因分型檢測(cè) 經(jīng)受檢者本人知情同意后,采集受檢者的口腔黏膜上皮細(xì)胞,利用硅膠吸附方法抽提樣本的基因組DNA。采用熒光定量PCR技術(shù)分別檢測(cè)分析葉酸代謝相關(guān)的3個(gè)DNA單核苷酸多態(tài)性位點(diǎn)(MTHFR C677T、A1298C和MTRR A66G)。每個(gè)反應(yīng)體系10 μL:包含1 μL濃度為20 mg/L的DNA模板,5 μL Taqman Universal Master Mix,0.5 μL Taqman-MGB探針,3.5 μL去離子水。其中,MTHFR C677T、A1298C與MTHRR A66G具體探針信息見表1,相關(guān)儀器、試劑均購(gòu)自美國(guó)ABI公司。反應(yīng)條件為95℃預(yù)熱10 min;92℃變性15 s,60℃延伸1 min,20個(gè)循環(huán);89℃變性15 s,60℃延伸1 min 30 s;30個(gè)循環(huán)。反應(yīng)完成后,用ABI7900型熒光定量PCR儀讀取樣品的終點(diǎn)熒光,利用分析軟件確定各個(gè)樣本的基因分型結(jié)果。
Tab.1 Detection sequences of gene MTHFR and MTRR表1 Taqman-MGB探針?biāo)谖恢?/p>
1.2.2 血漿Hcy水平檢測(cè) 對(duì)其中110例孕期女性檢測(cè)其血漿Hcy水平??崭钩槿∈軝z查者肘正中靜脈血3 mL,注入EDTA抗凝血管,混勻后靜置30 min后3 000 r/min離心10 min,分離血清于EP管,采用化學(xué)發(fā)光法測(cè)定Hcy。Hcy檢測(cè)試劑盒購(gòu)自德國(guó)BAYER公司。
1.3 統(tǒng)計(jì)學(xué)方法 采用SPSS 19.0軟件進(jìn)行統(tǒng)計(jì)學(xué)分析,應(yīng)用HaploView 4.2軟件進(jìn)行單核甘酸多態(tài)性的Hardy-Weinberg平衡、連鎖不平衡水平和單倍型結(jié)構(gòu)分析。計(jì)量資料以±s表示,比較采用方差分析;計(jì)數(shù)資料采用例(%)表示,比較采用χ2檢驗(yàn)。檢驗(yàn)水準(zhǔn)α=0.05。
2.1 Hardy-Weinberg平衡分析 對(duì)收集到的湘潭市女性MTHFR C677T、A1298C和MTRR A66G位點(diǎn)的檢測(cè)數(shù)據(jù)進(jìn)行Hardy-Weinberg遺傳平衡檢驗(yàn),χ2值分別為0.39、0.05和0.19,P>0.5。說明樣本具有本區(qū)域群體代表性。
2.2 湘潭市女性MTHFR C677T、A1298C和MTRR A66G位點(diǎn)基因多態(tài)性分布特點(diǎn)
2.2.1 MTHFR C677T位點(diǎn)基因多態(tài)性的分布特點(diǎn) 湘潭市女性的MTHFR C677T位點(diǎn)的TT基因型頻率為12.6%,高于惠州、瓊海,低于淄博、鄭州、煙臺(tái)、鎮(zhèn)江(均P<0.01)。與松滋相比差異無統(tǒng)計(jì)學(xué)意義,見表2。
2.2.2 MTHFR A1298C位點(diǎn)基因多態(tài)性的分布特點(diǎn) 湘潭市女性MTHFR A1298C位點(diǎn)的CC基因型頻率為4.8%,低于瓊海,高于淄博、鄭州、煙臺(tái)、鎮(zhèn)江、松滋(均P<0.05);與惠州差異無統(tǒng)計(jì)學(xué)意義(P>0.05),見表3。
2.2.3 MTRR A66G位點(diǎn)基因多態(tài)性的分布特點(diǎn) 湘潭市女性MTRR基因A66G位點(diǎn)的GG基因型頻率為6.8%,高于淄博,低于瓊海(P<0.05),與其他地區(qū)差異無統(tǒng)計(jì)學(xué)意義,見表4。
Tab.2 Comparison of MTHFR C677T genotype distribution and frequencies in different areas表2 不同地區(qū)漢族女性MTHFR C677T基因型頻率分布比較 例(%)
Tab.3 Comparison of MTHFR A1298C genotype distribution and frequencies in different areas表3 不同地區(qū)漢族女性MTHFR A1298C基因型頻率分布比較 例(%)
Tab.4 Comparison of MTRR A66G genotype distribution and frequencies in different areas表4 不同地區(qū)漢族女性MTRR A66G基因型頻率分布比較 例(%)
2.3 MTHFR C677T和A1298C兩位點(diǎn)連鎖情況及單倍型分析 單倍型分析表明,存在4種組合:CA (43.4%)、TA(34.9%)、CC(21.6%)、TC(0.1%)。兩位點(diǎn)間存在強(qiáng)連鎖不平衡現(xiàn)象(D’=0.986),見表5。
Tab.5 Comparison of MTHFR C677T and A1298C linkage analysis among Han women in Xiangtan city表5 湘潭市漢族女性MTHFR C677T和A1298C連鎖型分布 例(%)
2.4 血漿Hcy濃度與MTHFR C677T位點(diǎn)、A1298C位點(diǎn)以及MTRR基因A66G位點(diǎn)基因多態(tài)性的關(guān)系 3種MTHFR C677T基因型的Hcy水平差異有統(tǒng)計(jì)學(xué)意義,分別是TT型>CT型>CC型(P<0.05);3種MTHFR A1298C基因型的Hcy水平差異有統(tǒng)計(jì)學(xué)意義,分別是CC型>AA型>AC型(P<0.05)。MTRR基因A66G位點(diǎn)不同基因型的血漿Hcy水平差異無統(tǒng)計(jì)學(xué)意義,見表6。
Tab.6 Analysis of variance of concentration of plasma Hcy and MTHFR C677T,A1298C and MTRR A66G gene polymorphism表6 3種基因不同基因型的血漿Hcy濃度比較(mol/L,±s)
Tab.6 Analysis of variance of concentration of plasma Hcy and MTHFR C677T,A1298C and MTRR A66G gene polymorphism表6 3種基因不同基因型的血漿Hcy濃度比較(mol/L,±s)
*P<0.05;a與(1)比較,b與(2)比較,P<0.05
MTHFR C677T基因型CC(1)CT(2)TT(3)F n Hcy n Hcy MTHFRA 1298C基因型AC(1)AA(2)CC(3)Hcy n 4.98±1.76 7.09±3.16 4.98±2.67 2.424 47 46 17 5.71±0.18 5.94±1.47a8.52±2.01ab4.932*37 68 5 5.55±1.75 6.35±2.13a9.83±2.26ab3.811*MTRR A66G基因型AA(1)AG(2)GG(3)60 42 8
湖南省是出生缺陷高發(fā)區(qū),近十年出生缺陷發(fā)生率逐年上升,從2003年的124.33/萬到2012年的204.96/萬。其中,先天性心臟病占66.89%(第1位),總唇腭裂占12.51%(第4位),神經(jīng)管缺陷占3.57%(第10位)[15]。遺傳因素是出生缺陷的重要影響因素,MTHFR基因C677T位點(diǎn)的多態(tài)性會(huì)造成其編碼的氨基酸發(fā)生改變,MTHFR C677T位點(diǎn)為TT基因型是神經(jīng)管畸形發(fā)生的遺傳高風(fēng)險(xiǎn)因素,TT基因型比CC基因型人群的MTHFR酶活性下降60%~70%[16]。且MTHFR C677T和A1298C存在協(xié)同作用,導(dǎo)致MTHFR酶活性降低,影響葉酸代謝,使Hcy水平升高,與先天性心臟病等多種出生缺陷相關(guān)。
MTHFR兩位點(diǎn)存在強(qiáng)連鎖不平衡,與貴州布依族和苗族人群的報(bào)道類似[17]。湘潭市漢族女性MTHFR C677T、A1298C和MTRR A66G位點(diǎn)多態(tài)性分布與其他地區(qū)漢族女性存在差異,可能與人群對(duì)不同疾病的易感性有關(guān)。MTHFR C677T位點(diǎn)T等位基因頻率呈現(xiàn)北方高南方低的趨勢(shì),與我國(guó)出生缺陷發(fā)病率北方高南方低的趨勢(shì)一致。研究表明,T基因型女性在未服用葉酸增補(bǔ)劑及低葉酸飲食的情況下,其胎兒唇腭裂的發(fā)生風(fēng)險(xiǎn)均會(huì)增加,若以上兩種情況同時(shí)存在,則風(fēng)險(xiǎn)進(jìn)一步增高。反之,如果能夠補(bǔ)服葉酸增補(bǔ)劑、提高飲食中葉酸的含量則可以降低胎兒唇腭裂的發(fā)生風(fēng)險(xiǎn)[18]。
通過對(duì)不同MTHFR和MTRR酶活性組Hcy水平的比較,表明MTHFR的基因多態(tài)性導(dǎo)致的酶的活性降低是Hcy水平升高的危險(xiǎn)因素。由于基因多態(tài)性導(dǎo)致MTHFR酶活性降低后,體內(nèi)Hcy向甲硫氨酸的轉(zhuǎn)化會(huì)受到限制,導(dǎo)致血漿Hcy水平升高。Hcy具有細(xì)胞毒性,可以使巰基氧化,細(xì)胞內(nèi)產(chǎn)生大量氧自由基,損傷血管內(nèi)皮細(xì)胞并增加血栓形成的傾向,影響子宮胎盤血流,導(dǎo)致胎兒生長(zhǎng)發(fā)育的異常。
目前的孕期保健措施是從孕前3個(gè)月到孕早期3個(gè)月,每天增補(bǔ)葉酸0.4 mg。對(duì)于那些由基因多態(tài)性造成葉酸代謝障礙的人群,在補(bǔ)充相同劑量葉酸的情況下,紅細(xì)胞葉酸的濃度較正常人低,Hcy水平明顯升高。因此,通過對(duì)育齡女性進(jìn)行遺傳篩查,針對(duì)存在葉酸代謝障礙的遺傳風(fēng)險(xiǎn)人群,采取增加營(yíng)養(yǎng)素補(bǔ)充、加強(qiáng)紅細(xì)胞葉酸水平監(jiān)測(cè)、提高產(chǎn)前篩查和孕期管理依從性等干預(yù)措施,是有效達(dá)到出生缺陷及孕期疾病一級(jí)預(yù)防目的的重要方法,也是提高人口素質(zhì)的必要手段。
[1]Chinese Birth Defect prevention Report(2012)[J].China Pharmacy, 2012,39:3693.[衛(wèi)生部發(fā)布《中國(guó)出生缺陷防治報(bào)告(2012)》[J].中國(guó)藥房,2012,39:3693.]
[2]Moore LL,Bradlee ML,Singer MR,et al.Folate intake and the risk of neural tube defects an estimation of dose-response[J].Epidemiology,2003,14(2):200-205.
[3]He XM,Zhang Q,Yang Q,et al.Study on the methylenetetrahydrofolate reductase and methionine synthase reductase polymorphism [J].Chinese Journal of Family Planning,2010,18(1):13-18.[賀憲民,張群,楊琦,等.亞甲基四氫葉酸還原酶和甲硫氨酸合成酶還原酶基因多態(tài)性研究[J].中國(guó)計(jì)劃生育學(xué)雜志,2010,18(1):13-18.]
[4]Sun LJ,Zhang Y.Relationship between polymorphismin enzyme genes involving folate metabolism and risk of down syndrome[J]. Journal of International Rerroductive Health/Family Planning,2011, 03:240-242.[孫立娟,張穎.葉酸代謝相關(guān)酶基因多態(tài)性與唐氏綜合征[J].國(guó)際生殖健康/計(jì)劃生育雜志,2011,03:240-242.]
[5]Tamura T,Picciano MF.Folate and Human Reproduction[J].Am J Clin Nutr,2006,83(5):993-1016.
[6]Pei LH.Relationship of plasma homocysteine and the gene polymorphism of metabolic enzymes with neural tube defects[D].Central South University,2011.[裴利花.同型半胱氨酸及其代謝酶基因多態(tài)性與神經(jīng)管畸形發(fā)生的關(guān)系[D].中南大學(xué),2011.]
[7]Liu YH,Chen Y.The relationship between folate metabolism related gene and birth defects,poor pregnancy[J].Chinese Journal of Birth Health&Heredity,2012,8:6-8.[劉英華,陳瑛.葉酸代謝基因與出生缺陷和不良妊娠的關(guān)系[J].中國(guó)優(yōu)生與遺傳雜志2012,8:6-8.]
[8]Cong YY,Lu YQ,Rui XY,et al.Study on the Methylenetetrahydrofolate Reductase and Methionine Synthase Reductase Polymorphism among the Han women in Zibo City[J].Progress in Obstetrics and Gynecology,2012,21(10):779-781.[從玉英,魯衍強(qiáng),芮欣憶,等.淄博市漢族女性亞甲基四氫葉酸還原酶和甲硫氨酸合成酶還原酶基因多態(tài)性分布研究[J].現(xiàn)代婦產(chǎn)科進(jìn)展,2012,21 (10):779-781.]
[9]He YX,Gong JM,Shen Y,et al.The Study of Folic Acid Usage in Women of Childbearing Age in Henan Province[J].Chinese Journal of Clinical Pathologist,2012,4(1):6-10.[何燕霞,鞏姣梅,沈勇, 等.河南省育齡女性葉酸利用能力現(xiàn)狀研究[J].實(shí)用檢驗(yàn)醫(yī)師雜志,2012,4(1):6-10.]
[10]Yan Q,Lu YQ,Li Y,et al.Polymorphisms of MTHFR and MTRR in Women of Chinese Han Population in Yantai City[J].Journal of Shandong University(Health Sciences),2014,52(1):79-84.[嚴(yán)倩,魯衍強(qiáng),李瑛,等.煙臺(tái)市漢族女性性MTHFR和MTRR基因多態(tài)性的分布特征[J].山東大學(xué)學(xué)報(bào),2014,52(1):79-84.]
[11]Yang Y,Lu YQ,Rui XY,et al.Study on the MTHFR and MTRR Polymorphisma Among the Han Women in Zhenjiang City[J].ACTA Universitatis Medicinalis Nan Jing(Natural Science),2012,32(9): 1250-1253.[楊彥,魯衍強(qiáng),芮欣憶,等.鎮(zhèn)江市漢族女性MTHFR 和MTRR基因多態(tài)性分布研究[J].南京醫(yī)科大學(xué)學(xué)報(bào):自然科學(xué)版,2012,32(9):1250-1253.]
[12]Luo XL,Lu YQ,Guo WZ,et al.Geographical Distribution of MTHFR C677T,A1298C and MTRR A66G Gene Polymorphisms among the Han Gestational Age Women in Songzi City[J].Journal of Public Health and Preventive Medicine,2014,25(2):29-32.[羅秀莉,魯衍強(qiáng),郭文竹,等.湖北松滋市漢族女性MTHFR與MTRR基因多態(tài)性分布[J].公共衛(wèi)生與預(yù)防醫(yī)學(xué),2014,25(2):29-32.]
[13]Gao LJ,Lu YQ,Rui XY,et al.Polymorphism Distribution of Methylenetetrahydrofolate Reductase and Methionine Synthase Reductase among the Han Women in Huizhou[J].Journal of SUN YAT-SEN University(Medical Sciences),2013,34(1):140-143.[高利潔,魯衍強(qiáng),芮欣憶,等.惠州市漢族女性亞甲基四氫葉酸還原酶和甲硫氨酸合成還原酶基因多態(tài)性分布研究[J].中山大學(xué)學(xué)報(bào)(醫(yī)學(xué)科學(xué)版),2013,34(1):140-143.]
[14]Yan ZM,Lu YQ,Li Y,et al.Polymorphisms of MTHFR and MTRR among the Han Nationality Women in Qionghai City[J].Journal of Hainan Medical University,2013,19(1):18-20.[顏珠苗,魯衍強(qiáng),李瑛,等.瓊海市漢族女性MTHFR和MTRR基因多態(tài)性分布研究[J].海南醫(yī)學(xué)院學(xué)報(bào),2013,19(1):18-20.]
[15]Xie DH,Du QY,Wang H.Analysis the trend of birth-defects in Hunan Pro from 2003 to 2012[J].Chinese Journal of Birth Health and Heredity,2013,11:72-74.[謝冬華,杜其云,王華.湖南省2003年-2012年出生缺陷發(fā)生率變化趨勢(shì)分析[J].中國(guó)優(yōu)生與遺傳雜志, 2013,11:72-74.]
[16]Han IB,Kim OJ,Ahn JY,et al.Association of methylenetetrahydrofolate reductase(MTHFR 677C>T and 1298A>C)polymorphisms and haplotypes with silent brain infarction and homocysteine levels in a Korean population[J].Yonsei Med J,2010,51(2):253-260.
[17]Zhang T,Xie Y,Li Y,et al.Methlenetetrahydrofolate Reductase Polymorphism in Three Nationality in Guizhou[J].Chongqing Medicine,2013,42(28):3413-3415.[張婷,謝淵,李毅,等.貴州3個(gè)民族亞甲基四氫葉酸還原酶基因的遺傳多態(tài)性[J].重慶醫(yī)學(xué), 2013,42(28):3413-3415.]
[18]Ali A,Singh SK,Raman R.MTHFR 677TT alone and IRF6 820GG together with MTHFR 677CT,but not MTHFR A1298C,are risks for nonsyndromic cleft lip with or without cleft palate in an Indian population[J].Genet Test Mol Bioma,2009,13(3):355-360.
(2014-04-25收稿 2014-07-23修回)
(本文編輯 閆娟)
Relationship of Plasma Homocysteine with Gene Polymorphisms of MTHFR and MTRR among Han Women in Xiangtan City
WANG Shuyuan1,LU Yanqiang2,MA Shaojie2△,HUANG Jingxi1,YANG Kaiyun1,XIONG Min1,ZHOU Yuzhen1,YANG Qi3
1 Xiangtan Maternal and Child Health Hospital,Hunan 411100,China;2 Shanghai Institute of Target Molecules;3 National Center for Women and Children’s Health,Chinese Center for Disease Control and Prevention△
E-mail:mashaojie@genechina.com
ObjectiveTo investigate the relationship of plasma homocysteine with the genotype distribution of MTHFR and MTRR among Chinese Han women in Xiangtan.MethodsMTHFR C677T,A1298C and MTRR A66G genotyping was analyzed to detect the distribution of gene polymorphisms among 1 701 women from Xiangtan city then the data were compared with the rest of the Han women in Zibo,Zhengzhou,Yantai,Zhenjiang,Songzi,Huizhou,Qionghai.Plasma Hcy levels from 110 patients were measured and analyzed the correlation with gene polymorphisms.ResultsThe frequency of MTHFR C677T genotype and allele frequencies in Xiangtan is 12.6%which is higher than Huizhou(10.9%)and Qionghai (6.1%)but lower than Zibo(43.6%),Zhengzhou(36.8%),Yantai(32.2%),Zhenjiang(21.8%)with statistically significant difference(P<0.05).There is no significant different in MTHFR C677T between Xiangtan and Songzi.The frequency of MTHFR A1298C genotype and allele frequencies in Xiangtan is 4.8%which is lower than Qionghai(7.1%)but higher than Zibo (1.4%),Zhengzhou(2.4%),Yantai(1.8%),Zhenjiang(3.5%)and Songzi(2.6%)with statistically significant difference. The frenquency of MTRR A66G genotype and allele frequencies in Xiangtan is 6.8%which is higher than Zibo(4.8%)but lower than Qionghai(9.3%)with statistically signifcant difference.Plasma Hcy concentration correlate with MTHFR C677T, Hcy concentration in TT population is higher than that in CT and CC population(μmol/L:8.52±2.01 vs 5.94±1.47 vs 5.71± 0.18);Plasma Hcy concentration also correlate with MTHFR A1298C and Hcy concentration in CC population is higher than AA and AC population(μmol/L:9.83±2.26 vs 6.35±2.13 vs 5.55±1.75);Plasma Hcy concentration does not correlate with MTRR A66G.ConclusionThe gene polymorphism of MTHFR C677T,A1298C and MTRR A66G among the Hanwomen in Xiangtan was statistically different from other selected regions of China.Mutation in MTHFR C677T and A1298C were associated with elevated plasma levels of Hcy.
methylenetetrahydrofolate reductase;methionine synthase reductase;polymorphism;homocysteine
R715.5
A
10.3969/j.issn.0253-9896.2014.12.015
中國(guó)疾病預(yù)防控制中心婦幼保健中心婦幼保健分子遺傳醫(yī)學(xué)研究專項(xiàng)計(jì)劃(FY-ZX-ZD-0018)
1湖南省湘潭市婦幼保健院(郵編411100);2上海靶向分子醫(yī)學(xué)研究所;3中國(guó)疾病預(yù)防控制中心婦幼保健中心△
E-mail:mashaojie@genechina.com