2型糖尿病微血管病变患者血浆同型半胱氨酸的变化及其机制的探讨

目的 了解血浆同型半胱氨酸（Hcy)与2型糖尿病微血管病变（DMAP）间的关系，并分析影响糖尿病（DM）患者Hcy代谢的因素。方法 157例DM患者分为三组：无微血管并发症组（NDC）、糖尿病视网膜病变组（DR）和糖尿病肾病（DN）组；正常对照组（CON）组28例。测定血浆Hcy、叶酸、维生素B12浓度，并以PCR－RFLP技术检测亚甲基四氢叶酸还原酶（MTHFR）C667T突变和蛋氨酸合成酶还原酶（MSR）A66G突变率。结果 DM各组血Hcy浓度及空腹高Hcy血症发生率高于CON组，DN组又高于NDC组（P＜0．05）。DM患者血Hcy浓度与MTHFR BB基因型、BMI、HbAlc、FBG、PBG、二甲双胍的使用呈正相关，与血浆叶酸和VitB12呈明显负相关，与MSR基因型无关。多元逐渐回归分析结果显示，VitB12、HbA1c、MTHFR基因型和叶酸是DM患者血Hcy浓度的影响因素。结论 空腹高Hcy因症是DMAP的危险因子；2型DM中MTHFR基因型、VitB12、叶酸以及代谢紊乱的程度影响Hcy的浓度。     

血清同型半胱氨酸及亚甲基四氢叶酸还原酶基因多态性与2型糖尿病合并脑梗死的相关性研究

目的探讨血清同型半胱氨酸(Hcy)水平与亚甲基四氢叶酸还原酶(MTHFR)基因多态性对T2DM患者发生脑梗死的影响。方法对81例T2DM合并脑梗死(T2DM+脑梗死)组及325例单纯T2DM(T2DM)组血清Hcy、叶酸水平及MTHFR基因多态性等项目行统计学分析。结果 T2DM+脑梗死组与T2DM组MTHFR基因第677位T等位基因率及TT突变基因率分别为64.15%、60.15%和42.5%、34.5%(P>0.05)。TT型Hcy水平为(14.4±7.86)mmol/L,而CC型血清Hcy水平为(10.58±3.37)mmol/L,两基因型比较,差异有统计学意义(P<0.01)。结论 MTHFR基因多态性与T2DM患者发生脑梗死无相关性;MTHFR基因C677T突变基因型与高Hcy血症相关。     

MTHFR基因G1793A多态性与青年动脉粥样硬化血栓性脑梗死的相关性研究

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因G1793A多态性与青年动脉粥样硬化血栓性脑梗死(ATCI)的关系。方法选择50例青年ATCI病人作为病例组,同期健康体检者30名作为对照组,应用高通量测序技术检测MTHFR G1793A基因多态性,电化学发光免疫分析技术测定血清叶酸、维生素B12和同型半胱氨酸(Hcy)水平。结果病例组病人血清Hcy水平明显高于对照组(P0.05),两组MTHFR基因1793位点AA纯合型基因携带者的血清Hcy水平均明显高于GA杂合型和GG野生型基因携带者(P0.05),而GA杂合型和GG野生型基因携带者间的血清Hcy水平差异无统计学意义(P0.05)。结论 MTHFR基因G1793A多态性与血清Hcy水平有相关性,AA纯合型变异可能导致血清Hcy水平升高,但MTHFR基因G1793A多态性与青年ATCI无明显相关性,血清Hcy水平与青年ATCI有相关性。     

急性脑梗死患者MTHFR基因多态性与血浆同型半胱氨酸水平的关系

目的 探讨急性脑梗死（ACI）患者N5,N10-亚甲四氢叶酸还原酶（MTHFR）基因多态性与血浆同型半胱氨酸（Hcy）水平的关系.方法 采用多聚酶链反应2-限制性内切酶片段长度多态性技术（PCR2-RFLP）检测48例ACI患者MTHFR基因C677T位点多态性,同时测定血浆总Hcy及血清叶酸、维生素B12、尿酸（UA）.结果 ACI患者MTHFR基因T/T型频率为35.43％,T/C型频率为56.32％,C/C型频率为8.25％;T等位基因频率为63.59％,C等位基因频率为36.41％.MTHFR基因T/T型ACI患者血浆Hcy显著高于其他两型,T/C型与C/C型血浆Hcy水平较比较无显著差异.Hcy中度与轻度增高者MTHFR基因分布比较,P≤0.05.3组基因型间叶酸、维生素B12及UA水平均无显著差异.结论 ACI患者MTHFR基因C677T突变与Hcy水平显著相关,MTHFR基因纯合突变可能是引起高Hcy的一个重要遗传因素.     

同型半胱氨酸及代谢酶基因遗传多态性、叶酸和维生素B12与溃疡性结肠炎的相关性

目的探讨同型半胱氨酸(Hcy)及代谢酶基因遗传多态性、叶酸和维生素B12与溃疡性结肠炎(UC)的相关性。方法选择UC患者60例为观察组,选取同期健康体检人员60例作为对照组。观察两组Hcy、亚甲基四氢叶酸还原酶(MTHFR)及甲硫氨酸合成酶(MS)的基因多态性及叶酸和维生素B12水平。结果观察组Hcy为(14.74±1.69)mol/L,高于对照组〔(10.26±1.48)mol/L,P<0.05〕。观察组叶酸和维生素B12分别为(5.10±0.43)ng/ml和(241.63±10.51)pg/ml,均低于对照组〔(6.28±0.75)ng/ml和(376.52±11.38)pg/ml,P<0.05〕。两组MTHFR和MS基因型频率及等位基因频率比较,差异具有显著性(P<0.05);观察组治疗后Hcy为(11.33±1.50)mol/L,低于对照组(P<0.05);观察组治疗后叶酸和维生素B12分别为(6.04±0.58)ng/ml和(312.75±11.49)pg/ml,均高于对照组(P<0.05)。结论 UC患者中Hcy升高,叶酸和维生素B12浓度降低,Hcy及代谢酶基因遗传多态性、叶酸和维生素B12可能与UC密切相关。     

MTHFR基因多态性与老年慢性肾衰竭的相关性

目的探讨亚甲基四氢叶酸还原酶(MTHFR)基因多态性与老年慢性肾衰竭(CRF)的相关性。方法 268例老年CRF患者为CRF组。另外选取同期健康体检人群250例为对照组。采用PCR基因芯片技术检测MTHFR C677 C/T基因多态性。CRF组每日口服叶酸、维生素B6和维生素B12治疗6个月。治疗前后,采集患者静脉血2 ml,检测同型半胱氨酸(Hcy)和肌酐(Scr),计算得到eGFR。结果 CC、CT和TT型基因频率在两组间差异有统计学意义(P<0. 05); CRF组T等位基因频率显著高于对照组(P<0. 05)。治疗前,MTHFR基因TT型血清Hcy水平显著高于CC、CT型(均P<0. 05),eGFR显著低于CC、CT型(P<0. 05);治疗前后血清Hcy水平和eGFR差值均显著低于CC、CT型(均P<0. 05)。MTHFR基因TT型心绞痛、心肌梗死、心力衰竭和总体心血管事件发生率显著高于CC、CT型(均P<0. 05)。结论 MTHFR T等位基因可能是武汉市老年人群发生CRF的一个易感基因,MTHFR基因TT型患者肾功能更差,叶酸补充治疗效果不佳。     

系统性红斑狼疮与高同型半胱氨酸血症的临床研究

目的　观察系统性红斑狼疮 (SLE)患者血浆中同型半胱氨酸 (Hcy)水平 ,分析影响Hcy的因素和某些心血管因素的变化。 方法　测定 2 7例SLE和 31名正常对照的Hcy、维生素B12 、叶酸、C反应蛋白 (CRP)、氧化低密度脂蛋白 (oxLDL)、一氧化氮 (NO)、丙二醛 (MDA)的水平和亚甲基四氢叶酸还原酶 (MTHFR)基因 6 77位的多态性。结果　①SLE组Hcy水平明显较对照组高 ,其差异有显著性 [SLE组 (19± 7) μmol/L ,对照组 (12± 4 ) μmol/L ,P <0 0 0 1];②Hcy与维生素B12 、叶酸呈负相关 ,相关系数分别为 - 0 76 7和 - 0 6 7,P <0 0 0 0 1;③MTHFR基因 6 77位CT的突变使Hcy水平升高 [CC型 (12 8± 6 2 ) μmol/L ,CT型 (16 0± 2 1) μmol/L ,TT型 (18 9± 5 7) μmol/L ,P<0 0 0 1];TT基因型是高Hcy血症的易感基因 ,相对危险度 (RR) =31 4 9,P <0 0 5 ;TT基因型是SLE的易感基因 ,RR =6 913,P <0 0 5 ;④Hcy水平与NO、MDA、oxLDL呈正相关 ,并与CRP呈正相关。结论　①SLE患者普遍有高Hcy血症。②导致高Hcy血症的原因包括叶酸、维生素B12 的水平降低和MTHFR基因的突变 ,TT型基因是Hcy异常升高的易感基因。③TT型基因也是SLE的易感基因。④高Hcy血症可能通过损伤血管内皮 ,大量产生氧自由基 ,加速低密度     

急性心肌梗死、急性脑梗死患者血清同型半胱氨酸、叶酸、维生素B12水平研究

目的观察急性心肌梗死、急性脑梗死患者血清同型半胱氨酸(homocysteine,Hcy)、叶酸及维生素B12水平,探讨Hcy水平与叶酸、维生素B12的相关性及Hcy与心脑血管事件相关性的差异。方法随机选取山西医科大学第二医院2010年10月—2011年10月急性心肌梗死患者60例为心梗组,急性脑梗死患者72例为脑梗组,体检中心同期健康体检者60例为对照组。分别测定3组血清Hcy、叶酸、维生素B12水平,并做组间比较、相关性分析和非条件logistic回归。结果心梗组Hcy高于对照组(P<0.05),叶酸、维生素B12低于对照组(P<0.05);脑梗组Hcy高于对照组(P<0.05),叶酸、维生素B12低于对照组(P<0.05);心梗组、脑梗组Hcy、叶酸、维生素B12差异无统计学意义(P>0.05)。血清Hcy水平与叶酸(rs=-0.379)、维生素B12(rs=-0.350)呈负相关(P<0.01)。Hcy水平升高是急性心肌梗死(OR=1.253,95%CI:1.138～1.380)、急性脑梗死(OR=1.317,95%CI:1.182～1.467)的危险因素,Hcy与脑梗死的相关性更强(β脑梗组0.275vs心梗组0.226)。结论急性心肌梗死、急性脑梗死患者血清Hcy水平升高,叶酸、维生素B12水平降低。血清Hcy水平升高与叶酸、维生素B12缺乏有关。高同型半胱氨酸血症是心脑血管事件发生的危险因素,Hcy与脑梗死的相关性更强。     

慢性肾衰竭血透患者N5, N10-亚甲基四氢叶酸还原酶基因多态性和血浆同型半胱氨酸水平的研究

目的研究血透患者N5, N10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性及血清叶酸、维生素B12 (Vit B12)水平与血浆总同型半胱氨酸(tHcy)的关系.方法运用聚合酶链反应-限制性内切酶片断长度多态性技术(PCR-RFLP),检测53例血透患者(HD组)及40例健康对照组(C组)的MTHFR基因多态性;用高效液相色谱法和荧光探测仪测定血浆tHcy水平;用免疫化学发光法测定血清叶酸、Vit B12水平.结果 (1)MTHFR基因型有3种,纯合子突变型(+/+)、杂合子突变型(+/-)、正常型(-/-).HD组中(+/+)型频率为30.2 %,(+/-)型频率为45.3%,(-/-)型频率为24.5%,T等位基因频率为52.8%,基因型分布和等位基因频率与C组比较差异无显著性.(2)HD组中98%的患者存在着高Hcy (＞15.0 μmol/L)血症,平均血浆 tHcy 水平显著高于C组(38.68 μmol/L 对15.47 μmol/L,P<0.01).(3)HD组中(+/+)型平均血浆tHcy水平高于(-/-)型(45.32 μmol/L 对28.44 μmol/L),两者差异具有显著性(P=0.038).(4)HD组血清叶酸、Vit B12均与血浆tHcy水平呈负相关(r=-0.377,P=0.005;r=-0.311,P=0.023).结论血透患者血浆tHcy水平升高不仅与患者尿毒症时对其清除及代谢障碍有关,还受到MTHFR基因多态性和叶酸、Vit B12水平的影响.     

单纯收缩期高血压患者同型半胱氨酸代谢关键酶基因多态性相关因子研究

目的　研究同型半胱氨酸代谢关键酶亚甲基 4 氢叶酸还原酶 (MTHFR)及胱硫醚 β 合成酶 (CBS)基因多态性及其代谢相关因子在收缩期高血压 (ISH)发病中的作用 ,寻找ISH的易感基因及中间表型。方法　从天津高血压防治区选取ISH患者 5 5例 ,对照组 46例 ,应用分子生物学方法对其进行MTHFRC6 77,CBSG919,T833,C341位点基因多态性检测 ,并同时测定血中同型半胱氨酸(Hcy)、叶酸、维生素B6 、维生素B1 2 浓度 ,并对结果进行相关性分析。结果　ISH组中MTHFR及CBS基因构成与对照组不同存在统计学差异 (P <0 0 5 )。ISH组中MTHFRT等位基因为 6 9 1% ,其发生率高于对照组 (P <0 0 1) ;CBS阳性等位基因发生率为 15 2 % ,与对照组不同。ISH组Hcy水平 [( 17 70± 8 5 0 ) μmol L]高于对照组 [( 10 6 5± 3 10 ) μmol L](P <0 0 5 )。而叶酸、维生素B6 、维生素B1 2 浓度与对照组相比明显降低 (P <0 0 5 )。ISH组中高同型半胱氨酸血症的发生率高于对照组 ,具有统计学差异 (P <0 0 5 ) ,ISH组及对照组三种基因型血浆Hcy水平的改变存在着相同的趋势 ,即突变型高于杂合型与野生型。但血压升高的水平与Hcy浓度之间并无同向性变化。Hcy水平的增高可以增加ISH的发病 ,叶酸在ISH的发病中具有负性作用。结论　Hcy代谢     

Effects of metformin or rosiglitazone on serum concentrations of homocysteine, folate, and vitamin B12 in patients with type 2 diabetes mellitus

OBJECTIVES: Metformin is widely used in patients with type 2 diabetes but may decrease vitamin B(12) levels and increase levels of homocysteine (Hcy), a cardiovascular risk factor. Rosiglitazone, a peroxisome proliferator-activated receptor-gamma agonist, may reduce markers of inflammation. We investigated whether 6 weeks' treatment with metformin or rosiglitazone affects serum concentrations of Hcy, folate, or vitamin B(12) in subjects with newly diagnosed type 2 diabetes compared with controls. METHODS: We examined 165 patients with type 2 diabetes. Fasting blood samples, a physical examination, and a complete medical history were performed at the beginning and at the end of the treatment. All blood samples were obtained after a 12-h fast. RESULTS: After treatment, metformin use was associated with an increase in levels of Hcy by 2.36 micromol/l and decreases in folate and vitamin B(12) concentrations by -1.04 ng/ml and -20.17 pg/ml. During rosiglitazone treatment, Hcy levels decreased by -0.92 micromol/l; folate and vitamin B(12) levels remained unchanged. Metformin and rosiglitazone significantly decreased levels of triglyceride (TG), low-density lipoprotein (LDL), total cholesterol (total-C), HbA1c, insulin, and homeostasis model assessment (HOMA). Metformin also significantly decreased body weight. In controls, there was no change in Hcy, folic acid, vitamin B(12), TG, LDL, total-C, HbA1c, insulin, or HOMA levels. Homocysteine change did not correlate with insulin, folate, or vitamin B(12) changes in the metformin and rosiglitazone groups. CONCLUSIONS: In patients with type 2 diabetes, metformin reduces levels of folate and vitamin B(12) and increases Hcy. Conversely, rosiglitazone decreases Hcy levels in this time period. The clinical significance of these findings remains to be investigated.     

Plasma homocysteine levels in patients with early coronary artery stenosis and high risk factors

The aim of this study was to study the relationship between plasma homocysteine (Hcy), folic acid, vitamin B12 and early coronary artery disease (early-CAD) and high coronary risk factors. The plasma Hcy levels of 58 cases with early-CAD and 31 subjects without CAD were measured using high-performance liquid chromatography (HPLC) with fluorescence detection. Plasma folic acid and Vitamin B12 levels were measured with radioassay method. The plasma Hcy level was significantly higher in the early-CAD patients than in the controls [(13.7 +/- 5.1) micromol/L vs (10.3 +/- 5.7) micromol/L]. The plasma folic acid and Vitamin B12 levels were significantly lower in the early-CAD patients than in the controls. The plasma Hcy level was higher in patients with more than 3 risk factors of CAD than in patients with 1 or 2 risk factors and in the controls [(17.3 +/- 5.1) micromol/ L vs (12.9 +/- 4.8) micromol/L, (7.8 +/- 2.5) micromol/L]. Other than gender, all classical coronary risk factors were related to the elevated Hcy level. Hcy levels were elevated in patients with early-CAD and with high risk factors. Hyperhomocysteinemia plays an important role in the pathogenesis of CAD.     

MTHFR C677T基因多态性对稳定性冠心病患者叶酸降低同型半胱氨酸治疗的影响

目的探讨MTHFR C677T基因多态性对河南中部汉族稳定性冠状动脉粥样硬化性心脏病(冠心病)患者叶酸降低同型半胱氨酸(Hcy)治疗的影响。方法连续入选2018年4月至2018年9月于许昌市中心医院心血管内科住院的冠心病患者362例,依据MTHFR C677T基因检测结果分为A(CC型)、B(CT型)、C(TT型)三组,三组患者均在冠心病二级预防治疗的基础之上给予叶酸片降低Hcy治疗。记录患者应用叶酸治疗前、治疗后1个月、3个月血浆Hcy的变化,计算三组治疗3个月时降低Hcy治疗有效率,并对影响降低Hcy治疗的因素进行二元logistic回归分析。结果A、B、C三组分别有81例(22.4%)、169例(46.7%)和112例(30.9%)患者,三组治疗前血浆Hcy水平差异无统计学意义(P>0.05);三组治疗1个月和3个月血浆Hcy水平均低于治疗前,且A组治疗1个月时血浆Hcy水平低于B组和C组,差异均有统计学意义(P<0.05)。A组治疗有效率高于B组和C组,差异有统计学意义(P<0.05)。二元logistic回归分析显示,CC型患者降低Hcy治疗有效的可能是TT型患者的2.626倍,有熬夜史患者降低Hcy治疗有效的可能是无熬夜史患者的44.3%。结论MTHFR C677T基因多态性对稳定性冠心病患者叶酸降低Hcy治疗有影响,患者在降低Hcy治疗时应改变熬夜习惯。     

Methylenetetrahydrofolate reductase (MTHFR) polymorphism (C677T) in relation to homocysteine concentration in overweight and obese Thais

We analyzed the association between MTHFR (C677T) gene polymorphism with serum concentrations of homocysteine, folate, and vitamin B12 in 37 male and 112 female overweight/ obese Thai volunteers (BMI > or = 25.00 kg/m2), and compared them with 23 male and 90 female control subjects (BMI = 18.5-24.99 kg/m2). Statistically significant higher levels of serum homocysteine were found in the overweight/obese subjects than the control subjects (p < 0.05). Serum folic acid levels in the overweight/obese subjects were significantly lower than the control subjects (p < 0.05). When the data were grouped according to homocysteine concentration and MTHFR gene polymorphism, there were significantly higher homocysteine concentrations in the overweight/obese subjects than the control subjects in wild type gene polymorphism (CC) in the hyperhomocysteine group (homocysteine >10.0 mmol/l) (p < 0.05), but in genotype polymorphism (CC, CT, TT) there were lower folic acid and vitamin B12 concentrations in the overweight/obese subjects than in the control subjects. In the hyperhomocysteine groups, there was no significant difference in the frequencies of MTHFR (C677T) gene polymorphism between the overweight/obese subjects and the control subjects. Folic acid and gene polymorphism were found to be significantly related to the overweight/ obese and control groups in logistic regression analysis (p < 0.05). The results support the supposition that folic acid is more important than vitamin B12.     

Lack of association between carotid intima-media thickness and methylenetetrahydrofolate reductase gene polymorphism or serum homocysteine in non-insulin-dependent diabetes mellitus

We assessed the contribution of the serum homocysteine (Hcy) level, an independent risk factor for vascular disease, and methylene tetrahydrofolate reductase (MTHFR) gene polymorphism to the variability of intimal-medial thickness (IMT) of the common carotid artery in middle-aged non-insulin-dependent diabetes mellitus (NIDDM) subjects. One hundred thirty NIDDM patients (60 males and 70 females) with a mean age of 53 +/- 10 years and a mean diabetes duration of 11.3 +/- 7.9 years were enrolled for the study. Exclusion criteria included liver, heart, kidney, or other major-organ disease. Fasting total serum Hcy, folate, and vitamin B12 and clinical chemistry analyte levels were measured. MTHFR polymorphism was determined by polymerase chain reaction (PCR). IMT and plaques or stenosis in the common carotid were measured by ultrasonography. Serum Hcy was inversely correlated with vitamin levels and was slightly higher in subjects with the Val/Val genotype versus Ala/Val and Ala/Ala (P = .02); no differences in genotype were found in subjects with folate or vitamin B12 at or above the median level. In univariate analysis, common carotid IMT was significantly associated with age (P = .00001), the body mass index ([BMI] P = .0003), uric acid (P = .004), systolic blood pressure (P = .03), glycemia (P = .03), and total cholesterol (P = .04). No significant association was found between serum Hcy or MTHFR polymorphism and IMT. In multiple regression analysis, age (P = .0001), uric acid (P = .03), glycemia, and the BMI (P = .05) were independently associated with IMT and explained about 42% of IMT variability. In 130 NIDDM patients without nephropathy, basal levels of serum Hcy, as well as MTHFR polymorphism, did not predict significant changes in common carotid IMT.     

Homocysteine concentration in primary and systemic sclerosis associated Raynaud's phenomenon

OBJECTIVE: To investigate whether patients with systemic sclerosis (SSc) have raised homocysteine (Hcy) plasma levels, thought to be an independent risk factor for vascular disease, and to study the relationship between Hcy and endothelial damage, and between Hcy and methylene-tetrahydrofolate reductase (MTHFR) genotypes, and patients' vitamin nutritional status, which are among the more frequent causes of hyperhomocysteinemia. METHODS: We measured Hcy, von Willebrand factor (vWF), folic acid, and vitamin B12 plasma levels and analyzed the frequencies of MTHFR mutations in 30 patients with SSc and 12 patients with primary Raynaud's phenomenon (RP); 29 healthy subjects served as controls. RESULTS: Patients with SSc had higher Hcy and vWF concentrations than those with RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.02 and p < 0.0001, respectively). Folic acid and vitamin B12 were lower in SSc than in RP (p < 0.01 and p < 0.02, respectively) or controls (p < 0.05). MTHFR genotype did not influence Hcy, folate, or vitamin B12 concentrations, but patients homozygous for the mutant gene had higher vWF levels. CONCLUSION: Patients with SSc, but not those with RP, had significantly higher Hcy and vWF plasma levels. Nutritional rather than inherited factors seem to have a pathogenic role in SSc hyperhomocysteinemia.     

同型半胱氨酸与叶酸、维生素B12及维生素B6的关系

目的　探讨正常人群血同型半胱氨酸 (Hcy)水平分布及Hcy与年龄和性别的关系 ,Hcy水平与叶酸 ,维生素B1 2 及维生素B6之间的关系。方法　应用高效液相色谱 (HPLC)荧光检测法测定6 88例正常人血浆Hcy水平 ,用放射免疫方法测定叶酸及维生素B1 2 水平 ,用 96孔板微生物学法测定血清维生素B6水平。结果　相关分析结果显示 :血浆Hcy水平在正常人中呈非正态分布 ,随年龄增长血浆Hcy水平增加 ,男性比女性高。血浆Hcy水平与维生素B6、维生素B1 2 及叶酸水平呈负相关 (r分别为 - 0 35 4 8,- 0 2 91 6 ,- 0 32 76 ,P值均 <0 0 1 )。高Hcy血症者较非高Hcy血症者其血维生素B6、维生素B1 2 及叶酸水平均明显降低 (P值均 <0 0 1 )。结论　正常人中增高的血浆Hcy浓度与体内的维生素水平低下有关。     

Association of plasma homocysteine with serum interleukin-6 and C-peptide levels in patients with type 2 diabetes

Hyperhomocysteinemia is an independent risk factor for atherosclerotic disease. Because serum markers of inflammation and the metabolic syndrome are also associated with atherosclerotic disease and insulin resistance, we investigated whether plasma homocysteine (Hcy) levels were associated with serum markers of inflammation and factors of metabolic syndrome in 223 elderly patients with type 2 diabetes mellitus. The levels of plasma Hcy and serum interleukin-6 (IL-6), high-sensitivity C-reactive protein, and C-peptide were measured. The C677T mutation of methylenetetrahydrofolate reductase (MTHFR) gene was detected using the polymerase chain reaction-restriction fragment length polymorphism method. The number of abnormal metabolic factors (presence of diabetes, blood pressure > or =130/85 mm Hg, triglycerides > or =150 mg/dL, high-density lipoprotein cholesterol <35 mg/dL (men) or <39 mg/dL (women), or body mass index >25 kg/m 2 ) was assessed. Elevated plasma Hcy levels correlated significantly with serum IL-6 ( r = 0.25, P < .001), C-peptide ( r = 0.22, P < .01), and the number of abnormal metabolic factors ( r = 0.20, P < .01), but not with C-reactive protein. Multiple linear regression analysis revealed that log-transformed IL-6, serum C-peptide, vitamin B12 , and creatinine were significant determinants of plasma Hcy levels. The correlation between Hcy and IL-6 levels was strongest in those with TT genotype of C677T MTHFR among 3 genotypes. The association between plasma Hcy and serum IL-6 levels supports the hypothesis that the activation of innate immunity is involved in the pathogenesis of arteriosclerosis in patients with diabetes mellitus who are homozygous for the TT genotype of C677T MTHFR.