Kelemen Linda E, Anand Sonia S, Hegele Robert A, Stampfer Meir J, Rosner Bernard, Willett Walter C, Montague Patricia A, Lonn Eva, Vuksan Vladimir, Teo Koon K, Devanesen Sudarshan, Yusuf Salim
Department of Health Sciences Research, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, USA.
Atherosclerosis. 2004 Oct;176(2):361-70. doi: 10.1016/j.atherosclerosis.2004.06.003.
Few studies have evaluated the associations of plasma homocysteine concentration, the methylenetetrahydrofolate reductase (MTHFR) C677T genotype and B vitamin concentration with intima media thickness (IMT) in multiethnic populations.
In the Study of Health Assessment and Risk in Ethnic groups (SHARE), we measured carotid IMT, fasting serum folate, serum B12, plasma pyridoxal-5'-phosphate (PLP) and plasma homocysteine and determined the MTHFR C677T genotype in a cross-sectional study of 818 South Asian, Chinese and European Canadians without previous history of CVD, cancer or diabetes during 1996-1998.
Plasma homocysteine was inversely related to serum folate, serum B12, plasma PLP, B vitamin supplement use and Chinese ethnicity, and was positively associated with hypertension, smoking, IMT, MTHFR 677T/T genotype and South Asian ethnicity. Although ethnicity was not a statistically significant modifier, among carriers of the MTHFR 677T/T genotype with serum folate < or =14 nmol/L compared to >14 nmol/L, plasma homocysteine was significantly higher among South Asians (50.9% increase, P < 0.001) and Europeans (52.4% increase, P < 0.001) but not Chinese (11.0% increase, P > 0.05). Plasma homocysteine > 11.7 micromol/L was associated with a 5.9% (95% CI: 1.9%, 10.0%) increase in IMT (approximately 0.04 mm) in the pooled-data analyses with similar increases noted in the ethnic-specific analyses. The 677T/T genotype was not associated with a significant change in IMT in the pooled-data analyses (2.7%; 95% CI: -1.7%, 7.2%) nor in ethnic-specific analyses compared to other genotypes, although there were only 63 677T/T homozygotes.
The combination of lower serum folate and the MTHFR 677T/T genotype is associated with increased plasma homocysteine among South Asians and Europeans, but the association is not evident among Chinese possibly because their serum folate may not have been low enough to compromise MTHFR activity. Plasma homocysteine > 11.7 micromol/L appears to be associated with a clinically important increase in IMT.
很少有研究评估血浆同型半胱氨酸浓度、亚甲基四氢叶酸还原酶（MTHFR）C677T基因型和B族维生素浓度与多种族人群内膜中层厚度（IMT）之间的关联。
在种族健康评估与风险研究（SHARE）中，我们测量了818名南亚、华裔和加拿大欧洲裔且无心血管疾病（CVD）、癌症或糖尿病病史者的颈动脉IMT、空腹血清叶酸、血清维生素B12、血浆磷酸吡哆醛（PLP）和血浆同型半胱氨酸，并确定了MTHFR C677T基因型。该研究为1996 - 1998年的横断面研究。
血浆同型半胱氨酸与血清叶酸、血清维生素B12、血浆PLP、B族维生素补充剂使用及华裔呈负相关，与高血压、吸烟、IMT、MTHFR 677T/T基因型及南亚裔呈正相关。尽管种族不是统计学上显著的修饰因素，但在血清叶酸≤14 nmol/L的MTHFR 677T/T基因型携带者中，与血清叶酸>14 nmol/L者相比，南亚裔（升高50.9%，P<0.001）和欧洲裔（升高52.4%，P<0.001）的血浆同型半胱氨酸显著升高，而华裔（升高11.0%，P>0.05）则不然。在汇总数据分析中，血浆同型半胱氨酸>11.7 μmol/L与IMT增加5.9%（95%CI：1.9%，10.0%）（约0.04 mm）相关，种族特异性分析中也有类似增加。在汇总数据分析中，677T/T基因型与IMT的显著变化无关（2.7%；95%CI：-1.7%，7.2%），与其他基因型相比，在种族特异性分析中也无显著变化，尽管677T/T纯合子仅有63例。
血清叶酸水平较低与MTHFR 677T/T基因型的组合与南亚裔和欧洲裔血浆同型半胱氨酸升高有关，但在华裔中这种关联不明显，可能是因为他们的血清叶酸可能未低到足以损害MTHFR活性。血浆同型半胱氨酸>11.7 μmol/L似乎与IMT临床上重要的增加有关。
