Department of Medical and Surgical Critical Care, University of Florence, Viale Morgagni 85, 50134 Florence, Italy.
Thromb Haemost. 2010 Aug;104(2):231-42. doi: 10.1160/TH09-11-0748. Epub 2010 May 10.
The hypothesis underlying this study is that variations in genes involved in methionine metabolism may contribute to genetic susceptibility for early-onset ischaemic stroke. We investigated 58 polymorphisms in AHCY, BHMT, BHMT2, CBS, ENOSF1, FOLH1, MTHFD1, MTHFR, MTR, MTRR, NNMT, PON1, PON2, SLC19A1, SHMT1, TCN2, TYMS genes on genomic DNA from 501 young patients who survived ischaemic stroke and 1,211 sex and age comparable controls. Genotype distribution was significantly different between patients and controls for the following SNPs: rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, rs202680 FOLH1, rs2274976 MTHFR, rs1979277 SHMT1, rs20721958 TCN2. On multiple logistic regression analysis adjusted for traditional risk factors, rs10037045 BHMT, rs682985 BHMT2, rs1051319 CBS, and rs202680 FOLH1 remained independent risk factors for stroke. After haplotype reconstruction, generalised linear model analyses adjusted for traditional risk factors and using the FDR multiple testing correction showed significant associations between ischaemic stroke and BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS haplotypes. This study identifies significant genetic associations between premature ischaemic stroke and haplotypes in BHMT, CBS, FOLH1, MTR, PON2, TCN2 and TYMS genes involved in methionine metabolism.
本研究的假设是，参与蛋氨酸代谢的基因变异可能导致早发性缺血性中风的遗传易感性。我们研究了 501 名幸存缺血性中风的年轻患者和 1211 名性别和年龄匹配的对照者的基因组 DNA 中的 AHCY、BHMT、BHMT2、CBS、ENOSF1、FOLH1、MTHFD1、MTHFR、MTR、MTRR、NNMT、PON1、PON2、SLC19A1、SHMT1、TCN2、TYMS 基因中的 58 个多态性。患者和对照组之间的基因型分布在以下 SNP 中存在显著差异：rs10037045 BHMT、rs682985 BHMT2、rs1051319 CBS、rs202680 FOLH1、rs2274976 MTHFR、rs1979277 SHMT1、rs20721958 TCN2。在调整传统危险因素的多元逻辑回归分析中，rs10037045 BHMT、rs682985 BHMT2、rs1051319 CBS 和 rs202680 FOLH1 仍然是中风的独立危险因素。在进行单体型重建后，调整传统危险因素的广义线性模型分析并使用 FDR 多重测试校正显示，BHMT、CBS、FOLH1、MTR、PON2、TCN2 和 TYMS 单体型与缺血性中风之间存在显著关联。本研究确定了 BHMT、CBS、FOLH1、MTR、PON2、TCN2 和 TYMS 基因中与蛋氨酸代谢相关的单体型与早发性缺血性中风之间存在显著的遗传关联。
