OBJECTIVETo investigate methylenetetrahydrofolate reductase (MTHFR) gene C677T mutation and plasma homocysteine (Hcy) levels in Uygur patients with venous thromboembolism (VTE) in Xinjiang.

METHODSA total of 222 VTE patients including 74 Uygur and 148 Han ethnic patients were examined, and 86 Uygur ethnic and Han 134 ethnic healthy people were included as controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was applied to detect MTHFR gene C677T polymorphism and plasma Hcy levels were measured by fluorescence polarization immunoassay.

RESULTSThe MTHFR gene C677T genotypes distribution in Uygur VTE patients and control groups were: TT [28.38% (35/86) vs. 12.79% (11/86), P < 0.05], CT [41.89% (31/74) vs. 52.33% (45/86), P > 0.05]and CC [29.73% (22/74) vs. 34.88% (30/86), P > 0.05], respectively; and in Han VTE patients and control groups were: TT[27.03% (40/148) vs. 14.92% (20/134), P < 0.05], CT [44.59% (66/148) vs. 52.99% (71/134), P > 0.05] and CC [28.38% (42/148) vs. 32.09% (43/134), P > 0.05], respectively. SNP genotyping distribution frequency in Uygur and Han ethnic population was similar between controls and between VTE patients (P > 0.05). Plasma levels of Hcy in MTHFR gene TT genotype were statistically higher than CT and CC genotype (P < 0.05). After adjusting for age, gender, smoking history, hyperlipidemia, hypertension, diabetes, and MTHFR genotype, multifactor logistic regression analysis showed that plasma Hcy level (OR = 1.025, 95%CI 1.003 - 1.046, P = 0.024) and obesity (OR = 4.660, 95%CI 1.417 - 15.324, P = 0.011) were independent risk factors for Uygur ethnic patients with VTE while plasma Hcy level (OR = 1.020, 95%CI 1.006 - 1.034, P = 0.004) and smoking (OR = 2.867, 95%CI 1.062 - 6.586, P = 0.024) were independent risk factors for Han ethnic patients with VTE.

CONCLUSIONMTHFR C677T polymorphism (TT genotype carrier) and increased plasma levels of Hcy are risk factors for Uygur and Han ethnic patients with VTE in Xinjiang.

Adult ; Aged ; Asian Continental Ancestry Group ; genetics ; Ethnic Groups ; genetics ; Female ; Gene Frequency ; Genotype ; Homocysteine ; blood ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2) ; genetics ; Middle Aged ; Oxidoreductases Acting on CH-NH Group Donors ; genetics ; Polymorphism, Single Nucleotide ; Risk Factors ; Venous Thromboembolism ; blood ; genetics

BACKGROUNDIncreased levels of interleukin-6 (IL-6) and C-reactive protein (CRP) have been reported in patients with venous thromboembolisms (VTE). However, prospective studies did not confirm an association between IL-6, CRP and their polymorphism with the risk of VTE.

METHODSOne hundred and forty patients (including 66 males and 74 females, mean age (55.55 ± 17.11) years) and one hundred and sixty controls (including 74 males and 86 females, mean age (56.58 ± 12.24) years) were involved. An enzyme linked immunosorbent assay (ELISA) method was used for detecting the serum levels of inflammatory factors IL-6 and CRP in both groups. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used for analyzing the distribution of polymorphisms at the -572C/G and -597G/A sites of the promoter of the IL-6 gene and at 1059G/C of the CRP gene.

RESULTSSerum levels of IL-6 and CRP were significantly higher in the VTE group than in the control group (P < 0.05). The frequencies of -572C/G promoter polymorphisms CC, CG, and GG in the IL-6 gene were found to be 34%, 48%, and 18%, respectively, and the derived allele frequencies for the C and G alleles were 58% and 42%. There was a significant difference in the -572C/G promoter polymorphisms between the VTE group and control group (P < 0.05). For the -597G/A polymorphism, individuals all carried the GG and GA type; AA genotypes were not detected. The frequency of the GG, GC, and CC genotypes at the CRP1059G/C promoter was 87.57%, 7.86% and 3.57% in VTE group, while 86.25%, 10%, and 3.75% in control group, respectively. The frequency of G and C alleles at CRP 1059G/C was 91.43% and 8.57% in VTE group and 91.56% and 8.44% in the control group. The results showed that there was no statistically significant difference of 1059G/C genotype and mutation frequency of the allele between the VTE group and control group (P > 0.05). Multiple Logistic regression analysis showed CC homozygotes of the IL-6 -572G/C, body mass index (BMI), and CRP, IL-6, and high-density lipoprotein cholesterol (HDL-C) were independent risk factors for VTE (P < 0.05).

CONCLUSIONSWe found that VTE was associated with IL-6 and CRP levels, and there was an association of IL-6 and its promoter polymorphism at -572G/C with the risk of VTE. Thus far, a causal relationship between inflammation and VTE remains to be clarified and more prospective data are required.

Adult ; Aged ; C-Reactive Protein ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Interleukin-6 ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic ; genetics ; Venous Thromboembolism ; genetics