Abstract：
We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.
摘要：
我们评估了血浆同型半胱氨酸（HC）和亚甲基四氢叶酸还原酶（MTHFR）C677T多态性（rs1801133）的TT基因型在镰状细胞病（SCD）和相关的血管闭塞危象（VOC）和缺血性中风（IS）中的相关性。我们在Embase和Medline22项关于血浆HC的研究和22项关于MTHFR基因型的研究中确定。由于与年龄相关的HC差异，将成人和儿科SCD分开：879名成人SCD和834名对照（CTR）产生中性效应大小；427名儿科SCD和625CTR偏爱SCD（p=0.001），具有广泛的异质性（I2=95.5％），并按国家分组：六项研究（荷属安的列斯群岛n=1，美国n=5）产生中性效应大小，四个(印度n=1，阿拉伯国家n=3)赞成SCD(p<0.0001)。此外，VOC中的249个SCD和VOC中的419个产生中性效应大小。267例SCD中MTHFRTT基因型的合并患病率等于1199CTR（4.26％与2.86%,p=0.45),在84个SCD中，IS等于没有IS的86个SCD(5.9%与3.7%,p=0.47）；删除一项儿科研究产生了显着的效应大小（p=0.006）。中东和印度儿科SCD血浆HC较高，可能是由于维生素缺乏。尽管SCD患病率较低，MTHFRTT基因型与成人IS有关。
