CAJ | 학술논문

目的:探讨早产和低出生体重与母亲和婴儿5-10亚甲基四氢叶酸还原酶基因(MTHFR)C677T多态性的关系.方法:采用病例对照及核心家系的研究设计,共调查了500个核心家系,包括250个正常孕周出生的核心家系和250个早产核心家系.采用盐沉淀法提取基因组DNA,通过聚合酶链式反应(PCR)对5-10亚甲基四氢叶酸还原酶基因C677T多态性进行基因型鉴定.通过SAS软件的广义线性模型(GENMOD),选用对数线性模型(Log-linear Model)中的泊松回归进行最大拟然比检验(Maximum Likelihood Ratio Test),分析母亲和婴儿MTHFR基因分别与早产和低出生体重的关系.结果:首先,我们采用TDT方法分别检验了早产和低出生体重对照核心家系MTHFR 677T等位基因传递是否平衡,研究结果表明MTHFR 677T突变等位基因传递符合孟德尔遗传规律.之后,我们分析了MTHFR基因与早产和低出生体重的关系.结果显示:婴儿MTHFR CT 和TT基因型不但增加早产的发生危险性且具有显著的统计学意义(CT基因型:OR＝2.01,95%CI为1.21～3.32;TT基因型:OR为1.82,95%CI为1.02～3.26),而且婴儿MTHFR基因能够增加低出生体重的发生危险且具有显著的统计学意义(CT基因型:OR＝1.87,95%CI为1.08～3.24;TT基因型:OR＝1.90,95%CI为1.02～3.54).但是母亲MTHFR基因对早产和低出生体重的影响均没有显著的统计学意义.我们进一步观察了母亲与婴儿MTHER基因之间的交互作用对早产和低出生体重的影响,研究结果表明母亲与婴儿MTHFR基因之间无明显交互作用存在.结论:婴儿MTHFR基因CT和TT基因型能够增加早产和低出生体重发生风险且有显著的统计学意义,在早产核心家系中MTHFR677T突变等位基因不符合孟德尔遗传规律,可能是导致早产的遗传易感位点,并且MTHFR 基因有可能通过孕周的缩短(早产)而导致低出生体重这一生殖结局的发生.
목적:탐토조산화저출생체중여모친화영인5-10아갑기사경협산환원매기인(MTHFR)C677T다태성적관계.방법:채용병례대조급핵심가계적연구설계,공조사료500개핵심가계,포괄250개정상잉주출생적핵심가계화250개조산핵심가계.채용염침정법제취기인조DNA,통과취합매련식반응(PCR)대5-10아갑기사경협산환원매기인C677T다태성진행기인형감정.통과SAS연건적엄의선성모형(GENMOD),선용대수선성모형(Log-linear Model)중적박송회귀진행최대의연비검험(Maximum Likelihood Ratio Test),분석모친화영인MTHFR기인분별여조산화저출생체중적관계.결과:수선,아문채용TDT방법분별검험료조산화저출생체중대조핵심가계MTHFR 677T등위기인전체시부평형,연구결과표명MTHFR 677T돌변등위기인전체부합맹덕이유전규률.지후,아문분석료MTHFR기인여조산화저출생체중적관계.결과현시:영인MTHFR CT 화TT기인형불단증가조산적발생위험성차구유현저적통계학의의(CT기인형:OR＝2.01,95%CI위1.21～3.32;TT기인형:OR위1.82,95%CI위1.02～3.26),이차영인MTHFR기인능구증가저출생체중적발생위험차구유현저적통계학의의(CT기인형:OR＝1.87,95%CI위1.08～3.24;TT기인형:OR＝1.90,95%CI위1.02～3.54).단시모친MTHFR기인대조산화저출생체중적영향균몰유현저적통계학의의.아문진일보관찰료모친여영인MTHER기인지간적교호작용대조산화저출생체중적영향,연구결과표명모친여영인MTHFR기인지간무명현교호작용존재.결론:영인MTHFR기인CT화TT기인형능구증가조산화저출생체중발생풍험차유현저적통계학의의,재조산핵심가계중MTHFR677T돌변등위기인불부합맹덕이유전규률,가능시도치조산적유전역감위점,병차MTHFR 기인유가능통과잉주적축단(조산)이도치저출생체중저일생식결국적발생.
To investigate the association of the C677T polymorphism of the 5,10-methyleneterahydrofolate reductase(MTHFR) gene with preterm delivery(PTD) and low birth weight (LBW). Methods: A total of 250 normal gestational age families and 250 PTD families were enrolled in the study. Polymerase Chain Reaction (PCR) followed by restriction enzyme digestion were used for genotyping the polymorphism of MTHFR C677T. A Maximum Likelihood Ratio Test approach based on the log-linear model was used to analyze the relationship of MTHFR gene polymorphism and risk of PTD and LBW. Results: Firstly, we checked the Mendelian transmissions of the variant alleles of MTHFR 677T in PTD and LBW control-parent-triads using TDT test, respectively. These analyses of controls support Mendelian transmission. When children's genotypes were considered, the MTHFR CT and TT genotypes could significantly increase the risk of PTD and LBW, compared to the genotype of MTHFR CC, the odds ratio and 95% confidence interval (CI) for MTHFR CT and TT genotypes were 2.01,1.21-3.32;1.82, 1.02-3.26 in PTD group, and were 1.87, 1.08-3.24; 1.90, 1.02-3.54 in LBW group respectively. When mother's genotypes were considered, the MTHFR gene polymorphism was not associated with PTD and LBW. Meanwhile, we also examined the association of mothers' and children's combined genotypes of MTHFR C677T with the risk of PTD and LBW, and did not find any significant interaction between mothers' and children's genotypes. Conclusion: The infant MTHFR CT and TT genotypes are responsible for mothers' PTD and LBW in our study population. It supports that the non-Mendelian transmission among preterm children is due to a causal association between the MTHFR 677T variant alleles and preterm delivery,and MTHFR gene likely affects LBW via shortened gestation (PTD).