Association of methionine synthase reductase gene polymorphism with unexplained recurrent spontaneous abortion

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Author:
GUO Qian-nan(Medical Genetics Institute, Henan Province People's Hospital, Zhengzhou 450003, China)
LIAO Shi-xiu(Medical Genetics Institute, Henan Province People's Hospital, Zhengzhou 450003, China)
KANG Bing(Medical Genetics Institute, Henan Province People's Hospital, Zhengzhou 450003, China)
ZHANG Ju-xin()
WANG Rui-li()
DING Xue-bing(Medical Genetics Institute, Henan Province People's Hospital, Zhengzhou 450003, China)
ZHANG Wei-hua()
Journal Title:
Chinese Journal of Obstetrics and Gynecology
Issue:
Volume 47, Issue 10, 2012
DOI:
10.3760/cma.j.issn.0529-567x.2012.10.006
Key Word:
Ferredoxin-NADP reductase ; Abortion, habitual ; Polymorphism, genetic ;Polymerase chain reaction

Abstract: Objective To explore the relationship between the polymorphism of methionine synthase reductase(MTRR) A66G and the susceptibility to unexplained repeated spontaneous abortion (URSA).Methods Total of 200 Henan Han couples with URSA (URSA group) and 76 Henan Han healthy couples without URSA (control group)were enrolled in this study.Their MTRR A66G genotypes were determined by PCR restriction fragment length polymorphism (PCR-RFLP).Results (1) The allele frequencies of MTRR A66G:the frequencies of allele A and allele G in URSA group were 76.5% (153/200)in husband and 72.8% (146/200) in wife,23.5% (47/200) in husband and 27.2% (54/200) in wife,respectively.The frequencies of allele A and allele G in control group were 78.9% (60/76) in husband and 78.3% (59/76) in wife,21.1% (16/76) in husband and 21.7% (16/76) in wife,respectively.The frequencies of allele A and allele G were not significantly different between female and male subjects within the same experimental group (P > 0.05),and also there were not significantly different between the same gender subjects at URAS and control groups(P > 0.05).(2) The genotype frequencies of MTRR A66G:the frequencies of genotype AA,AG and GG in URSA group were 57.0% (114/200) in husband and 52.0% (104/200) in wife,39.0% (78/200) in husband and 41.5% (83/200) in wife,4.0% (8/200) in husband and 6.5% (13/200) in wife,prepectively.The frequencies of genotype AA,AG and GG in control group were 59.2% (45/76) in husband and 59.2% (50/76) in wife,39.5% (30/76) in husband and 38.2% (29/76) in wife;1.3 % (1/76) in husband and 2.6% (2/76) in wife,prepectively.The frequencies of genotype AA,AG and GG were not significantly different between female and male subjects within the same group (P > 0.05),and also there were not significantly different between the same gender subjects at URSA and control groups (P >0.05).(3) Combined genotype of couples:the combined genotype frequencies of GG + GG,GG + AG,GG +AA,AG + AG,AG + AA and AA + AA in URSA group were 1.0% (2/200),2.5% (5/200),6.0% (12/200),20.0% (40/200),38.0% (76/200),and 32.5 % (65/200),prepectively ; the combined genotype frequencies in control group were 0,1.3% (1/76),2.6% (2/76),17.1% (13/76),42.1% (32/76),36.8% (28/76),prepectively.The combined genotype analysis between the two groups were also not significantly different (P > 0.05).Conclusion The polymorphism of MTRR A66G gene was not associated with the susceptibility to URSA (P > 0.05),and so it was not the inherited genetic risk factor of URSA.

  • [1]Swanson DA,Liu ML,Baker PJ,et al.Targeted disruption of the methionine synthase gene in mice.Mol Cell Biol,2001,21:1058-1065.
  • [2]Elmore CL,Wu X,Leclerc D,et al.Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase.Mol Genet Metab,2007,91:85-97.
  • [3]Rosenblatt DS,Cooper BA,Pottier A,et al.Altered vitamin B12 metabolism in fibroblasts from a patient with megaloblastic anemia and homocystinuria due to a new defect in methionine biosynthesis.J Clin Invest,1984,74:2149-2156.
  • [4]Steen C,Rosenblatt DS,Scheying H,et al.Cobalamin E (cblE) disease:a severe neurological disorder with megaloblastic anaemia,homocystinuria and low serum methionine.J Inherit Metab Dis,1997,20:705-706.
  • [5]Zavadáková P,Fowler B,Suormala T,et al.cblE type of homocystinuria due to methionine synthase reductase deficiency:functional correction by minigene expression.Hum Mutat,2005,25:239-247.
  • [6]Matthews RG,Elmore CL.Defects in homocysteine metabolism:diversity among hyperhomocystinemias.Clin Chem Lab Med,2007,45:1700-1703.
  • [7]Desouza C,Keebler M,McNamara DB,et al.Drugs affecting homocysteine metabolism:impact on cardiovascular risk.Drugs,2002,62:605-616.
  • [8]Guenther BD,Sheppard CA,Tran P,et al.The structure and properties of methylenetetrahydrofolate reductase from Escherichia coli suggest how folate ameliorates human hyperhomocysteinemia.Nat Struct Biol,1999,6:359-365.
  • [9]Yamada K,Chen Z,Rozen R,et al.Effects of common polymorphisms on the properties of recombinant human methylenetetrahydrofolate reductase.Proc Natl Acad Sci U S A,2001,98:14853-14858.
  • [10]林其德.原因不明复发性流产的基础与临床研究进展.中华妇产科杂志,2003,38:481-483.
  • [11]Blumenfeld Z,Brenner B.Thrombophilia-associated pregnancy wastage.Fertil Steril,1999,72:765-774.
  • [12]Murakami S,Matsubara N,Saitoh M,et al.The relation between plasma homocysteine concentration and methylenetetrahydrofolate reductase gene polymorphism in pregnant women.J Obstet Gynaecol Res,2001,27:349-352.
  • [13]李晓梅,张友忠,许燕雪,等.MTHFR基因C677T位点多态性与不明原因多发性自然流产的相关性.中华医学遗传学杂志,2004,21:39-42.
  • [14]Gaughan DJ,Kluijtmans LA,Barbaux S,et al.The methionine synthase reductase (MTRR) A66G polymorphism is a novel genetic determinant of plasma homocysteine concentrations.Atherosclerosis,2001,157:451-456.
  • [15]van der Linden IJ,den Heijer M,Afman LA,et al.The methionine synthase reductase 66A > G polymorphism is a maternal risk factor for spina bifida.J Mol Med(Berl),2006,84:1047-1054.
  • [16]Szvetko AL,Fowdar J,Nelson J,et al.No association between MTHFR A1298C and MTRR A66G polymorphisms,and MS in an Australian cohort.J Neurol Sci,2007,252:49-52.
  • [17]Rai PS,Murali TS,Vasudevan TG,et al.Genetic variation in genes involved in folate and drug metabolism in a south Indian population.Indian J Hum Genet,2011,17 Suppl 1:S48-53.
  • [18]Cai D,Ning L,Pan C,et al.Association of polymorphisms in folate metabolic genes and prostate cancer risk:a case-control study in a Chinese population.J Genet,2010,89:263-267.
  • [19]杜子明,黄爱玲,柳息洪.人蛋氨酸合成酶还原酶A66G基因突变频率的检测.解剖学研究,2004,26:112-114.
  • [20]笪伟,刘和俊.MTRR基因 A66G多态性及血浆同型半胱氨酸水平与心肌梗死的关系.安徽医科大学学报,2011,46:467-470.
  • [21]Biselli JM,Goloni-Bertollo EM,Haddad R,et al.The MTR A2756G polymorphism is associated with an increase of plasma homocysteine concentration in Brazilian individuals with Down syndrome.Braz J Med Biol Res,2008,41:34-40.
  • [22]Sunden SL,Renduchintala MS,Park El,et al.Betaine-homocysteine methyltransferase expression in porcine and human tissues and chromosomal localization of the human gene.Arch Biochem Biophys,1997,345:171-174.
  • [23]Deng L,Elmore CL,Lawrance AK,et al.Methionine synthase reductase deficiency results in adverse reproductive outcomes and congenital heart defects in mice.Mol Genet Metab,2008,94:336-342.
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