Frequency of mutations in “thrombophilic state” genes in Uzbekistan

The frequency of mutations in a number of genetic markers, specifically factor V gene (G1691A), blood coagulation factor II gene (G20210A), and the methylenetetrahydrofolate reductase (MTHFR) gene (C677T), is studied in ethnic Uzbek patients with deep vein thrombosis of the lower extremities and in healthy donors. It is established that the incidence of mutant alleles among patients in Uzbekistan for FV Leiden is 12.9%; for prothrombin, 4%; and for MTHFR, 47.8%. The mutant allele C677T of the MTHFR gene has the highest expressivity in the appearance of MTHFR (47.8%). It is noted that this mutation in the MTHFR gene is encountered significantly more frequently in females with deep vein thrombosis than in males with deep vein thrombosis. The G20210A mutation in the prothrombin gene is encountered more rarely in the Uzbek population. The penetrance is studied and the role of these mutations in the appearance of deep vein thrombosis is estimated.     

Inherited thrombophilia genes in minorities

Mutations in several genes have recently been identified which predispose to thrombosis, specifically Factor V G1691A (Factor V Leiden), Prothrombin G20210A, and Methylene tetrahydrofolate reductase (MTHFR) C677T. The prevalence of these genes in European populations has been studied, but there is little data on their prevalence in minorities. Samples from a predominantly African-American population were analyzed for these mutations. While the G20210A mutation in the prothrombin gene and homozygosity for the C677T mutation of the MTHFR were not found in African-Americans, it appears that the carrier rate for the MTHFR C677T among Hispanics may be higher than in other reported groups.     

Association of deep venous thrombosis with prothrombotic gene polymorphism identified in lung cancer cases

Venous thrombosis is a significant cause of morbidity and mortality in patients with malignancies. We aimed to investigate the association between prothrombotic gene polymorphisms detected in lung cancer cases and deep venous thrombosis (DVT). Totally 66 patients with an established diagnosis of lung cancer, of which 33 developed DVT, were enrolled. Multiplex PCR technique and reverse hybridization strip assay were performed on DNA extracted from peripheral blood, in order to analyze prothrombin G20210A, factor V G1691A, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, angiotensin converting enzyme (ACE), plasminogen activator inhibitor-1 (PAI-1), and glycoprotein IIIa (Gp IIIa) gene mutations. Among prothrombotic gene polymorphisms investigated in this study, the commonest ones were PAI-1 4G/5G (56% heterozygous, 39% homozygous) and ACE gene mutations (58% heterozygous, 17% homozygous). The presence of homozygous MTHFR A1298C mutation was significantly associated with DVT (P = 0.020). Comparing the lung cancer patients with and without DVT, only MTHFR A1298C gene polymorphism differed significantly (P = 0.040). We determined a higher rate of prothrombotic gene mutations in lung cancer patients who developed DVT. However, statistical significance was achieved only for MTHFR A1298C gene mutation. Therefore, nongenetic factors for disturbance of hemostatic metabolism should also be considered in lung cancer patients.     

Evaluation of Factor V G1691A,prothrombin G20210A,Factor XIII V34L,MTHFR A1298C,MTHFR C677T and PAI-1 4G/5G genotype frequencies of patients subjected to cardiovascular disease (CVD) panel in south-east region of Turkey

Cardiovascular disease (CVD) risk factors, such as arterial hypertension, obesity, dyslipidemia or diabetes mellitus, as well as CVDs, including myocardial infarction, coronary artery disease or stroke, are the most prevalent diseases and account for the major causes of death worldwide. In the present study, 4,709 unrelated patients subjected to CVD panel in south-east part of Turkey between the years 2010 and 2013 were enrolled and DNA was isolated from the blood samples of these patients. Mutation analyses were conducted using the real-time polymerase chain reaction method to screen six common mutations (Factor V G1691A, PT G20210A, Factor XIII V34L, MTHFR A1298C and C677T and PAI-1 ?675 4G/5G) found in CVD panel. The prevalence of these mutations were 0.57, 0.25, 2.61, 13.78, 9.34 and 24.27 % in homozygous form, respectively. Similarly, the mutation percent of them in heterozygous form were 7.43, 3.44, 24.91, 44.94, 41.09 and 45.66 %, respectively. No mutation was detected in 92 (1.95 %) patients in total. Because of the fact that this is the first study to screen six common mutations in CVD panel in south-east region of Turkey, it has a considerable value on the diagnosis and treatment of these diseases. Upon the results of the present and previous studied a careful examination for these genetic variants should be carried out in thrombophilia screening programs, particularly in Turkish population.     

Molecular Characterization of Factor V Leiden G1691A and Prothrombin G20210A Mutations in Saudi Newborns with Stroke

This study examined a possible association between the mutations related to Factor V Leiden and Factor II (prothrombin) and stroke in Saudi neonates. A multiplex PCR was established to detect Factor V Leiden G1691A and prothrombin G20210A mutations in 72 neonatal stroke subjects and 70 healthy adult controls with no family history of thromboembolic diseases. The frequency of the homozygous normal genotype (GG) of both genes was found to be significantly lower in the stroke subjects than in the controls (P < 0.0001). The stroke cases also had higher frequencies of the combined Factor II heterozygous mutant form (GA) and the homozygous normal Factor V (GG) (P < 0.0001) and of the combined heterozygous Factor V and the homozygous normal Factor II genotypes (GG) (P = 0.0) than controls. The study concluded that prothrombin and Factor V Leiden may be important risk factors for neonatal stroke in Saudi children.     

Thrombophilic gene polymorphism studies in G6PD deficient individuals from Saudi population

We performed a study to evaluate the role of three single nucleotide polymorphisms (SNPs), factor V Leiden G1691A (FVL), prothrombin gene mutation G20210A (PRT or FII-G20210A) and methylenotetrahydrofolate reductase variant C677T (MTHFRC677T), as risk factors for G6PD in Saudi populations. Our results did not show any association with the three Thrombophilic genes with FVL gene, no statistical analysis have shown any association with either allele or genotype frequencies OR=0.566, p=.0.667, (95% CI=0.014-22.48) and OR=0.569, p=0.251¸ (95% CI=0.014-22.96).In PRT gene G20210A for G Vs A, p=0.774; OR=0.566 (95%CI; 0.011-29.6); AA+GA Vs GG; p=0.502; OR=0.569 (95%CI=0.010-2969). G and A allele frequencies were similar between cases and controls with no statistical significance. In the MTHFR gene none of the genotypes or allele frequency cannot show any association OR=1.281, p=.0.667, (95% CI=0.414-3.958) and OR=1.1.172, p=0.800¸ (95% CI=0.343-4.008). Similarly, the difference of T allele frequencies between patients and controls was not found any association. In conclusion, our finding indicates that the prevalence of G1691A, G20210A and C677T mutations in G6PD deficient individuals is not statistically different compared to normal subjects and G6PD is not associated with these thrombophilic mutations in Saudi population.     

The prevalence of factor V Leiden,prothrombin G20210A and methylenetetrahydrofolate reductase polymorphism C677T among G6PD deficient individuals from Western Iran

It has been suggested that the allele frequency of thrombophilic mutations is affected by glucose-6-phosphate dehydrogenase (G6PD) deficiency. The prevalence of thrombophilic mutations were studied in sixty G6PD deficient individuals including 57 males and three females with the mean age of 15 ± 3.08 and 110 age and sex matched healthy individuals consisted of 95 males and 15 females with the mean age of 16.19 ± 2.17 from the Kermanshah Province of Iran. Using a combination of PCR-RFLP technique, single strand conformation polymorphism (SSCP) analysis and DNA sequencing polymorphic G6PD mutations were identified. The factor V Leiden, prothrombin G20210A and methylenetetrahydrofolate reductase (MTHFR) C677T were detected by PCR-RFLP method using MnlI, HindIII and HinfI restriction enzymes, respectively. Three mutations, G6PD Mediterranean, G6PD Chatham and G6PD Cosenza were identified in 60 G6PD deficient individuals with highest prevalence of G6PD Mediterranean (91.6%). In G6PD deficient individuals the prevalence of factor V Leiden tended to be higher (5%) compared to healthy individuals (2.7%). The prevalence of prothrombin G20210A mutation in G6PD deficient individuals was 1.7%. However, in normal subjects the prevalence of this mutation was 2.7%. The frequency of T allele in G6PD deficient individuals were insignificantly higher (29.16%) than those in healthy individuals (26.8%). Our finding indicates that the prevalence of factor V Leiden, prothrombin G20210A and MTHFR C677T in G6PD deficient individuals is not statistically different compared to normal subjects and G6PD deficiency is not associated with these thrombophilic mutations in Western Iran.     

Impact of hemostatic gene single point mutations in patients with non-diabetic coronary artery disease

Single point mutations in the genes coding for hemostatic factors were shown to be major inherited predisposing factors for venous thromboembolism. However, their contribution in the development of non-diabetic coronary artery disease [nDCAD] remains controversial. Angiographically demonstrated nDCAD patients (n = 86) and healthy controls (n = 90) were included in the study. Genotype analysis of hemostatic gene polymorphisms were assessed by using CVD strip assay, based on allele specific oligonucleotide probes. The carrier frequency of factor V (FV) H1299R, prothrombin G20210A, glycoprotein (Gp) IIIa L33P, plasminogen activator inhibitor-I (PAI-1) 4G/5G, 4G/4G, 5G/5G, methylenetetrahydrofolate reductase (MTHFR) A1298C and β-fibrinogen −455 G > A were similar between patients and controls. In contrast, frequency of FV Leiden was significantly higher among patients (12.5%) than controls (5%, OR: 7.94; 95%CI: 1.9–49.6) and FXIII V34L was significantly lower among patients (23.7%) than controls (40%, OR: 0.24; 95%CI: 0.1–0.89). In addition, the frequency of the MTHFR C677T polymorphism was 32.5% among patients compared with 42.5% in controls, of which the T/T genotype was significantly lower among patients (5%) than controls (17.5%, OR: 0.06; 95%CI: 0.01–0.58). No difference was observed in prevalence of prothrombin G20210A, FV H1299R, Gp IIIa L33P, PAI-1 4G5G, MTHFR A1298C, β fibrinogen 455 G > A mutations between patients and controls. However, lower frequency of FXIII Val34Leu and MTHFR C677T polymorphisms may decrease, while FV Leiden polymorphism may increase development of nDCAD.     

Allelic polymorphism of F2, F5 and MTHFR genes in population of Ukraine

Analysis of F2, F5 and MTHFR genes SNPs allelic variants in population of Ukraine. Polymorphic variants were analyzed in 172 unrelated individuals using PCR followed by RFLP analysis. Following genotypes have been identified: GG (97%), GA (3%) for F2 gene G20210A SNP, GG (96.5%), GA (3.5%) for F5 gene G1691A SNP and CC (49.5%), CT (43%), TT (7.5%) for MTHFR gene C677T SNP. Following combined genotypes have been detected. We observed 1.7% heterozygous carriers of MTHFR gene 677T SNP which were heterozygous for one of the alleles of F5 1691A or F2 20210A genes. On the other hand, the 7.5% MTHFR gene 677T SNP homozygous individuals carried wild type alleles only of F5 and F2 genes. None of the individuals was carrying F5 1691 A and F2 20210A genes polymorphic variants simultaneously. The data about F2, F5 and MTHFR genes SNPs allelic frequencies in the population of Ukraine have been obtained. Thus, distribution of F2, F5 and MTHFR genotypes based on analysis of SNP in those three genes simultaneously has been detected.     

Prevalence of factor V G1691A (Leiden) and prothrombin G20210A polymorphisms among apparently healthy Jordanians

Factor V Leiden and prothrombin G20210A are related genetic risk factors for venous thromboembolism (VTE). Analysis for both mutations is increasingly being performed on patients exhibiting hypercoagulability. The objective of this study was to determine the prevalence of factor V Leiden (FVL), prothrombin-G20210A (PT-G20210A) polymorphisms and their coexistence among apparently healthy Jordanians. One thousand apparently healthy individuals from representative regions of Jordan with no previous history of VTE participated in this study. The mean age of participants was 28.5+/-6.4 years (age range 18-45 years). Two hundred and eighteen subjects were APC resistant with an APC-R mean of 85.52+/-15.35 seconds; the non-resistant subjects had an APC-R mean of 159.90+/-26.96 seconds. A multiplex polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) for the simultaneous detection of FVL and prothrombin G20210A was used to analyze the 218 DNA samples that were APC-R resistant. Both mutations generate HindIII RFLPs and the prothrombin amplicon contains an invariant HindIII recognition sites. The multiplex PCR-RFLP of Factor V for those 218-samples was: 41 wild-type, 169 heterozygous mutant, and eight homozygous mutant individuals. For prothrombin G20210A, the multiplex PCR-RFLP identified 215 wild-type and three heterozygous mutant individuals. Factor V positive individuals (n=50) had a mean F-V activity of 78.04%+/-25.81. F-V activity among wild type (n=41), F-V Leiden heterozygous (n=169) and F-V Leiden homozygous (n=8) were 92.93%+/-16.17, 87.02%+/-15.21 and 96.14%+/-12.32, respectively. Factor II positive subjects (n=47) had a mean factor II activity of 127.96%+/-21.37. F-II activity among carriers (heterozygous, n=3) and non-carriers (normal, n=215) of PT-G20210A mutation were 107.67%+/-9.29 and 105.00%+/-17.79, respectively. The prevalence of FVL was 21.8% and there is a little likelihood of the co-inheritance of the FVL and PT-G20210A among healthy young adults, since only few cases were found to be carriers for the two alleles.     

Prevalence of coagulation factor II G20210A and factor V G1691A Leiden polymorphisms in Chechans, a genetically isolated population in Jordan

Background Coagulation factor II G20210A and coagulation factor V (Leiden) G1691A single nucleotide polymorphisms (SNPs) are major inherited risk factors of venous thromboembolism. In view of the heterogeneity in their world distribution and lack of sufficient information about their distribution among Chechans, we addressed the prevalence of these SNPs in the Chechan population in Jordan, a genetically isolated population. Methods and Results factor II G20210A and factor V Leiden SNPs were analysed by polymerase chain reaction and restriction fragment length polymorphism (PCR?CRFLP) method and Amplification refractory mutation detection system (ARMS) respectively in 120 random unrelated subjects from the Chechan population in Jordan. Among the subjects studied for factor II G20210A mutation there were three individuals carrying this mutation as heterozygous (one female and two male), giving a prevalence of 2.5?% and an allele frequency of 1.25?%. No homozygous factor II allele was found. Factor V Leiden G1691A mutation was detected as heterozygous in 22 of 120 of individuals (17 female and five male) indicating a prevalence of 18.3?% and allele frequency of 9.2?%. No homozygous allele was found. Conclusion Our results indicated that prevalence of factor II G20210A mutation in the Chechan population is similar to prevalence in Jordan and Caucasian populations (1?C6?%) while the prevalence of factor V Leiden was higher in the Chechan population compared to Jordan and Caucasian populations (2?C15?%).     

MTHFR C 677T mutation and 4G/5G PAI-1 polymorphism in patient with polycystic ovarian syndrome

Combined oral contraceptives (Ocs) are the most commonly used androgen suppressors and the treatment of choice for menstrual dysfunction in women with polycystic ovarian syndrome (PCOs). Although OCs have remained popular due to their convenience and effectiveness, there have been continuing concerns about adverse effects. The OCs have long been known to incur and increased risk of venous thromboembolism especially in carriers of common inherited thromboembolic defects. Factor V Leiden, prothrombin factor G20210A polymorphism, MTHFR (C677T) mutation and 4G/5G polymorphism of the PAI-1 gene account for the majority of thromboembolic events in association with oral contraceptive use. The aim of the article is to present woman with unrecognized inherited thrombophilia who was treated with OCs due to PCOs signs.     

High incidence of two methylenetetrahydrofolate reductase mutations (C677T and A1298C) in Hispanics

Mutations in the 5,10-methylenetetrahydrofolate reductase (MTHFR) and coagulation factors II and V genes have been found at high frequencies in European and American Caucasian populations and are associated with increased risk for thrombophilia, premature coronary artery disease, and a variety of adverse pregnancy outcomes. Hispanic populations in the United States exhibit high levels of some of these conditions, so we initiated a population-based study to determine the frequency of these mutations (MTHFR C677T and A1298C, Factor II G20210A and Factor V G1691A) in this group. We find comparable frequencies of the Factors II and V mutations, but a high incidence of the two MTHFR mutations in a diverse sample of American Hispanics compared to those reported in Caucasians. Prospective studies of Hispanic women with these mutations and pregnancy outcomes will establish if there is a causal relationship.     

Prevalence of myocardial infarction polymorphisms in Afyonkarahisar, Western Turkey

The aim of the study was to investigate relationship between polymorphisms in genes that are clinical and environmental features and the risk of myocardial infarction (MI) in Afyonkarahisar subjects living in Turkey. Prevalence of the several genes polymorphisms, ≤45 (42.04 ± 3.3) and ≥46 (57.19 ± 7.5) years were studied in individuals with MI and without MI (40.30 ± 9.01) individuals were studied. We tested 140 with MI individuals for factor V (FV) Leiden, FV H1299R, Prothrombin G20210A, factor XIII (FXIII) V34L, β-fibrinogen b-455G/A, plasminogen activator inhibitor-1 (PAI-1)-675 4G/5G, human platelet antigens 1 (HPA-1) a/b, apolipoprotein B (ApoB) R3500Q, apolipoprotein E (ApoE), E2, E3, and E4, angiotensin-converting enzyme (ACE) D/I, 5,10 methylenetetrahydrofolate reductase (MTHFR) 677C/T, and MTHFR 1298A/C polymorphisms using a ViennaLab CVD strip assay. This study results were compared without MI control groups. According to the our results, prothrombin, factor XIII and MTHFRC677T deletions were the most frequent genetic variants in risk groups of hyperlipidemic patients (value of odds ratio sequentially [OR] = 4.5, p = 0.05, [OR] = 2.16, p = 0.04 and [OR] = 2.8, p = 0.09). MTHFRA1298C and PAI-1 deletions were most frequent genetic variants in risk groups for MI in patients with diabetes mellitus (value of odds ratio sequentially [OR] = 3.79, p = 0.06 and [OR] = 5 × 10(8), p = 0.000). ACE deletions were positively associated with family history of cardiovascular events (OR = 3.62, p = 0.03). We found a strong relationship between genetic variants and risk factors. Significant associations between genetic variants predicting cardiovascular events and common risk factors (hyperlipidemia, smoking, diabetes mellitus and family history) patients were found.     

Allele polymorphism analysis of hemostasis and folate metabolism genes by real-time microchip PCR

Genetic diagnostics is widely used for detection of risk factors of hereditary thrombophilias caused by molecular defects in the coagulation system. The hereditary thrombophilias are frequently associated with higher incidences of point mutations in hemostasis (F2 20210G>A, F5 1691G>A) and folate metabolism (MTHFR 677C>T, MTHFR 1298A>C) genes. Combinations of gene abnormalities in F2 and/or MTHFR with Leiden mutation (F5 1691G>A) significantly increase risk of thrombosis. Thus, simultaneous analysis of allele polymorphism of these genes is of clinical importance. This study has demonstrated high efficiency of microchip-based multiplex real time PCR for analysis of allele specific polymorphism in hemostasis and folate metabolism genes. Using this test it is possible to analyze polymorphism of the three genes (four point mutations) in a short time; it requires a minimal quantity of DNA template and PCR reagents including DNA polymerase, and thus can be recommended for clinical laboratory diagnostics.     

Ethnic differences in the prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian prenatal population

Differences in the prevalence of thrombophilias in different ethnic populations have been demonstrated. Because the Australian population includes many different ethnic groups, we sought to assess the effect of ethnicity in our Australian prenatal population on the prevalence of thrombophilic polymorphisms. Asymptomatic, nulliparous women (n = 1,129) recruited for a large prospective study were included in this analysis. These women had no personal or family history of venous thromboembolism and were not known to be carrying an inherited or acquired thrombophilia. Ethnicity was determined at recruitment, and women were categorized as being of Northern European, Southern European, Middle Eastern, Asian, or Other ethnicity. These women underwent genotyping for the following polymorphisms: factor V Leiden G1691A, prothrombin gene A20210G mutation, methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C, and thrombomodulin C1418T. The factor V Leiden allele was seen significantly more frequently in patients of Middle Eastern background compared to those of Northern European and Asian ethnicity (p < 0.05). The prothrombin gene mutation was seen significantly more frequently in patients of Southern European ethnicity compared to those of Northern European or Asian ethnicity (p < 0.05). The MTHFR C677T allele (mutant) was significantly less common in those of Asian ethnicity compared to patients of Northern European and Southern European ethnicity (p < 0.0005). There were no significant differences seen with the MTHFR A1298C polymorphism. The mutant thrombomodulin allele was seen significantly more frequently in Asian women compared to Northern European, Southern European, or Middle Eastern women (p < 0.005). There are important ethnic differences in the prevalence of thrombophilic polymorphisms in the Australian prenatal population.     

5, 10-Methylenetetrahydrofolate reductase (MTHFR) 677 C --> T genetic polymorphism in 228 Croatian volunteers

5, 10-Methylenetetrahydrofolate Reductase (MTHFR) is one of the key enzymes in the metabolism of homocysteine, where it catalyses its remethylation. The autosomal recessive bp 677 C --> T mutation in the MTHFR gene leads to the substitution of valine for alanine. Individuals who are homozygous for this C677T mutation exhibit a decreased specific activity and increased thermolability of this enzyme. This leads to increased plasma levels of homocysteine, which is a known risk factor for atherosclerosis and various manifestations of the atherosclerotic disease. The aim of this study was to find out the distribution and frequency of this mutation in the general Croatian population. A group of 228 volunteers (175 males and 53 females) has been analyzed for the MTHFR polymorphism, which revealed the following distribution: 105 (46.05%) individuals were without mutation (C/C), 102 (44.74%) were heterozygous (C/T) and 21 (9.21%) homozygous (T/T). These findings are within the results of studies on other European populations.     

Rapid automated simultaneous screening of (G1691A) Factor V, (G20210A) prothrombin,and (C677T) methylenetetrahydrofolate reductase variants by multiplex PCR using fluorescence scanning technology

The Factor V Leiden mutation (G1691A), and mutations in the prothrombin (G20210A) and 5,10-methylenetetrahydrofolate reductase (C677T) genes are common hereditary risk factors associated with venous thrombosis. The aim of this study was to develop an automated, PCR-based genotyping assay for rapid simultaneous screening of these three mutations. We adapted multiplex PCR, using primer modifications to introduce cleavage sites for restriction endonucleases into the fragments bearing each of the mutations. The three mutations were analyzed in a single tube by fluorescence scanning. An internal digestion control was introduced to prevent false-negative results due to incomplete digestion or a total lack of digestion. DNA fragment analysis was carried out using an automated capillary electrophoresis instrument (ABI310). This reliable, efficient, easy-to-use assay can be applied to specimens from large clinical trials and epidemiological surveys.     

G20210A prothrombin gene mutation identified in patients with venous leg ulcers

The G20210A mutation variant of prothrombin gene is the second most frequent mutation identified in patients withdeep venous thrombosis, after factor V Leiden. The risk for developing deep venous thrombosis is high in patients identified as heterozygous for G20210A mutation. In order to identify this polymorphism in the gene coding prothrombin, the 345bp fragment in the 3'- untranslated region of the prothrombin gene was amplified using amplification by polymerase chain reaction and enzymatic digestion by HindIII (restriction endonuclease enzyme). The products of amplification and enzymatic's digestion were analized using agarose gel electrophoresis. We investigated 20 patients with venous leg ulcers and we found 2 heterozygous (10%) for G20210A mutation. None of the patients in the control group had G20210A mutation. Our study confirms the presence of G20210A mutation in the Romanian population. Our study also shows the link between venous leg ulcers and this polymorphism in the prothrombin gene.     

Methylenetetrahydrofolate reductase gene polymorphisms in 13 Chinese ethnic populations

It has been shown that the polymorphisms of Methylenetetrahydrofolate reductase (MTHFR) gene are associated with susceptibility to several disorders including hyperhomocysteinemia, vascular disease, birth defect, and certain cancers, and exhibit great diversities among various populations. The aim of this study was to investigate the prevalence of two common non-synonymous single nucleotide polymorphisms (i.e., C677T and A1298C) at MTHFR gene in 13 Chinese populations. A total of 1015 healthy individuals from 13 populations distributed widely from north to south in China were studied. DNA samples were isolated from peripheral blood samples and genotyped using polymerase chain reaction-restriction fragment length polymorphism. For C677T polymorphism, the frequency in Chinese of CC homozygous was 42.4%; CT heterozygous was 49.8%; and TT homozygous was 7.9%. For A1298C, AA homozygous was 39.2%; AC heterozygous was 38.6%; and CC homozygous was 22.2%. The allelic frequency of 677T and 1298C was 32.8 and 41.5%, respectively, and each allele frequency had significant variance in 13 Chinese populations. The frequency of the 677T allele among southern populations was 30.7% compared to 38.0% among northeastern and 30.5% among northwestern populations. The difference was statistically significant (p < 0.01). The frequency of 1298C mutation in southerns was 58.9% whereas in northeasterns it was 24.0% and 37.6% in northwesterns. This was also statistically significant (p < 0.01). The MTHFR C677T and A1298C sites were in linkage disequilibrium in the Chinese population revealed by our data.