Mohanty Pankaj K, Kapoor Seema, Dubey Anand P, Pandey Sanjeev, Shah Renuka, Nayak Hemant K, Polipalli Sunil K
Department of Pediatrics, LNJP, MAMC, New Delhi, India.
Indian J Hum Genet. 2012 Sep;18(3):285-9. doi: 10.4103/0971-6866.107977.
Evaluation of C677T polymorphisms of the methylenetetra hydrofolate reductase (MTHFR) gene and its association with level of serum homocysteine, folate, and vitamin B12 as possible maternal risk factors for Down syndrome.
This was a case-control study.
Fifty-two mothers (mean age 27.6 years) with babies having free trisomy 21 of North Indian ethnicity and 52 control nonlactating mothers (mean age 24.9 years) of same ethnicity attending services of genetic lab for bloodletting for other causes were enrolled after informed written consent. Fasting blood was collected and was used for determination of plasma homocysteine, vitamin B12, and folate (serum and RBC), and for PCR amplification of the MTHFR gene.
The prevalence of MTHFR C677T polymorphism in north Indian mothers of babies with trisomy 21 Down syndrome was 15.38% compared to 5.88 % in controls. The difference between two groups was not statistically significant (P = 0.124). Low serum folate was demonstrated in 34.62% of cases vs. 11.54% in controls, which was significant (P = 0.005). Low RBC folate was found in 30.7% of cases versus 11.53% in controls, which was not significant (P = 0.059), when analyzed independently. But on multiple regression analysis the difference was statistically significant. Low serum vitamin B12 was found in 42.31% of cases versus 34.62% in controls, which was not significant (P = 0.118). The mean serum homocysteine in cases was 10.35 ± 0.68 while controls were 9.02 ± 0.535.
Serum levels of folate were low in cases. The RBC folate levels were comparable in both groups. However the combined serum folate and RBC folate were low in cases compared to control groups. Homocysteine levels in our study were higher in Down syndrome mothers compared to controls; however high-serum level of Homocysteine had no association with MTHFR polymorphism. No association of serum vitamin B12 with MTHFR polymorphism in occurrence of Down syndrome births was found. Peri- or preconceptional folate supplementation may therefore lead to a decline in DS births, if supported by larger studies.
评估亚甲基四氢叶酸还原酶（MTHFR）基因的C677T多态性及其与血清同型半胱氨酸、叶酸和维生素B12水平的关联，这些可能是唐氏综合征的母体风险因素。
这是一项病例对照研究。
在获得知情书面同意后，招募了52名北印度族裔、孩子患有21号染色体三体游离型的母亲（平均年龄27.6岁）以及52名同种族、因其他原因到基因实验室采血的非哺乳期对照母亲（平均年龄24.9岁）。采集空腹血，用于测定血浆同型半胱氨酸、维生素B12和叶酸（血清和红细胞），以及进行MTHFR基因的PCR扩增。
患有21三体唐氏综合征婴儿的北印度母亲中MTHFR C677T多态性的患病率为15.38%，而对照组为5.88%。两组之间的差异无统计学意义（P = 0.124）。34.62%的病例血清叶酸水平低，而对照组为11.54%，差异有统计学意义（P = 0.005）。独立分析时，30.7%的病例红细胞叶酸水平低，而对照组为11.53%，差异无统计学意义（P = 0.059）。但经多元回归分析，差异有统计学意义。42.31%的病例血清维生素B12水平低，而对照组为34.62%，差异无统计学意义（P = 0.118）。病例组血清同型半胱氨酸的平均值为10.35±0.68，而对照组为9.02±0.535。
病例组血清叶酸水平低。两组红细胞叶酸水平相当。然而，与对照组相比，病例组合并的血清叶酸和红细胞叶酸水平低。在我们的研究中，唐氏综合征母亲的同型半胱氨酸水平高于对照组；然而，高血清同型半胱氨酸水平与MTHFR多态性无关。未发现血清维生素B12与唐氏综合征出生时MTHFR多态性之间存在关联。因此，如果有更大规模研究的支持，围孕期或孕前补充叶酸可能会导致唐氏综合征出生人数下降。
