In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic indiv...In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.展开更多
Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe o...Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.展开更多
This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest q...This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile （0R=0.11; 95% CI, 0.04-0.33; P〈0.05）. MTHFR 677 C〉T polymorphism was associated with the risk of ESCC by using chi-square tests （P〈0.05）. For the CT genotype, the risk of ESCC significantly increased in study participants with low serum folate concentrations （〈26.92μg/L） compared with participants with high serum folate concentrations （〉26.92 μg/L） by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.展开更多
Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T(MTHFR C677T)polymorphism and diabetic retinopathy(DR).Methods A total of 6971 subjects including 2707 DR patients and...Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T(MTHFR C677T)polymorphism and diabetic retinopathy(DR).Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study.A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR,and study quality was also assessed.Results Strong associations were observed between the MTHFR C677T polymorphism and DR.The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.6&2.55,and 2.31 respectively in allele contrast model(T vs.C,95%CZ:1.29-2.18,P<0.001,f=7&4%),homozygous model(TT vs.CC,95%CZ:1.70-3.83,P=0.008,72=54.4%)and dominant model(TT+CT vs.CC,95%CZ:1.62-3.29,P<0.001,12=74.7%).This association can also be found in contrast to the Ned(non-complicated diabetic mellitus)group(allele contrast,OR—1.50,95%Ch 1.07-2.11,P=0.032,I2=62.1%;homozygous,OR—2.39,9S%CZ:1.06-5.38,P=0.017,Z2=66.7%;dominant,OR=1.59,95%CZ:0.97-2.62,P=0.056,I2=56.5%).For the heterozygous model(CT vs.CC),the association was significant in contrast to the healthy control group(OR=1.46,95%CZ:1.64-3.69,P=0,P=77.3%),while in contrast to the Ned control group the association was not statistically meaningful(OR=1.38,95%CZ:0.87-2.18,P=0.131,Z2=43.7%).For the recessive model,1.92-fold increased risk was found only in contrast to the Ned control group(95%C1:1.07-3.43,P=0.064,P=55.0%).There was no significant association found in the models in contrast to the DM control group.Conclusion In this meta-analysis,we found an association between the MTHFR C677T polymorphism and DR,especially in contrast to the Ned control group.Further studies are required to establish more definite relationship.展开更多
Objective: Migraine, a common chronic neurological disorder involves a pathophysiology having both multiple genetic and environmental factors. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) involved in folate metab...Objective: Migraine, a common chronic neurological disorder involves a pathophysiology having both multiple genetic and environmental factors. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has an important role in a cell for folate availability which is critical for DNA integrity. Methods: This case-control study conducted in Srinagar, Kashmir (North India) between 2013 and 2015 was designed to evaluate risk induced due to MTH-FR 677C>T gene polymorphisms to contribute in susceptibility for migraine in Kashmir population (North India). Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we tested the genotype distribution of 100 migraine patients in comparison with 120 healthy migraine-free controls from the same geographical region. Results: The genotypic frequencies of the patients and controls were not significantly associated (p > 0.05). Higher distribution of TT mutant genotype was found in controls as against the cases (5% versus 1%) but association was not significant (p > 0.05). Per copy frequency of T allele (Val) was found to be 0.14 in cases versus 0.19 in controls (p 0.05). Similar scenario was observed when migraine without aura was compared with controls where variant genotype (16% cases versus 39.0% controls: p > 0.05) as well as allele frequency was found to be less in cases (cases 0.15 versus 0.19 controls: p > 0.05). Conclusions: We conclude that MTHFR gene C677T polymorphism has no role in predisposition to the migraine in our population and cannot serve as a predictive factor for the risk of migraine.展开更多
Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Although the clinical manifestations and the pathological features have been well elucidated, a clear etiology of AD is still unknown to t...Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Although the clinical manifestations and the pathological features have been well elucidated, a clear etiology of AD is still unknown to this day. In the past few decades, investigations have elucidated that both the genetic and the environmental factors are capable of causing the development of AD. We report a patient with clinically diagnosed earlyonset Alzheimer's disease, age of onset 45 years. Genetic analysis revealed two MTHFR heterozygous polymorphisms C677T and A1298C.展开更多
文摘In Africa, the prevalence of diabetes is escalating and remains a concern due to the numerous complications it causes. Vascular damage associated with diabetes leads to a prothrombotic state observed in diabetic individuals. Diabetes is a complex and multifactorial disease involving genetic components. With the aim of preventing complications and contributing to an efficient management of diabetes, we investigated genes likely to lead to a risk of thrombosis, in particular the C677T of MTHFR, G20210A of prothrombin, and R506Q of factor V Leiden in type 2 diabetics in Abidjan receiving ambulatory care. A descriptive cross-sectional study was carried out on consenting type 2 diabetic patients. Mutation detection was carried out using the PCR-RFLP method employing restriction enzymes. Hemostasis tests (fibrinogen, D-dimers, fibrin monomers, and von Willebrand factor) were performed using citrate tubes on the Stage? Star Max automated system. Plasminogen activator inhibitor was assayed by ELISA method, and biochemical parameters were determined using the COBAS C311. The study population consisted of 45 diabetic patients, 51.1% of whom presented vascular complications, mainly neuropathy. Disturbances in hemostasis parameters were observed, with 15.5% of patients showing an increase in fibrin monomers. Mutation analysis revealed an absence of factor V mutation (factor V Leiden) and of G20210A mutation of the prothrombin gene. However, 15.6% of subjects had a heterozygous C677T mutation of MTHFR, with 57% of them being anemic. The exploration of biological and genetic factors associated with thrombotic risk is of significant interest in the optimal management of African type 2 diabetics.
基金Acknowledgment This work was supported by the National High Tech- nology Research and Development Program of China （Grants 2004AA216090 and 2002BA711A08）, National Basic Research Program of China （Grant 2004Cb518805）, the Natural National Science Foundation of China （Grant 30470960） and the China Medical Board of New York.
文摘Aim： To analyze the distribution of the single nucleotide polymorphism （SNP） C677T in the methylenetetrahydrofolate reductase （MTHFR） gene in 355 infertile Chinese patients with idiopathic azoospermia or severe oligozoospermia and 252 fertile Chinese men as controls to explore the possible association of the SNP and male infertility. Methods： Using the polymerase chain reaction （PCR）-restriction fragment length polymorphism technique, the allele and genotype distribution of SNP C677T in the MTHFR gene were investigated in both patients and controls. Results： The frequencies of allele T （40.9% vs 30.4%, P = 0.002, odds ration [OR] = 1.58, 95% confidence interval [CI]： 1.24-2.02） and mutant homozygote （TT） （18.3% vs. 11.5%, P = 0.023, OR = 1.72, 95% CI： 1.07-2.76） as well as carrier with allele （TT ＋ CT） （63.4% vs. 49.2%, P = 0.0005, OR = 1.79, 95% CI： 1.29-2.48） in infertile patients were significantly higher than those in controls. After patient stratification, the significant differences in distribution of the SNP between each patient subgroup and control group still remained. Conclusion： Our findings indicate that there is an association of SNP C677T in the MTHFR gene with male infertility, suggesting that this polymorphism might be a genetic risk factor for male infertility in Chinese men.
基金supported by grants from the National Science Foundation of China(No.30800914 and No.81372985)Dietary Nutrition Research and Education Foundation of Danone(DIC2011-05)Program Granted for Scientific Innovation Research of College Graduate in Jiangsu Province Research Fund(CXZZ_0179)
文摘This study examined associations between MTHFR C677T polymorphism and serum folate concentrations with the risk of esophageal precancerous lesions （EPL） and esophageal squamous cell carcinoma （ESCC）. The highest quartile of serum folate concentration significantly decreased the risk of ESCC compared with the lowest quartile （0R=0.11; 95% CI, 0.04-0.33; P〈0.05）. MTHFR 677 C〉T polymorphism was associated with the risk of ESCC by using chi-square tests （P〈0.05）. For the CT genotype, the risk of ESCC significantly increased in study participants with low serum folate concentrations （〈26.92μg/L） compared with participants with high serum folate concentrations （〉26.92 μg/L） by using multinomial logistic regression models. The MTHFR genotype may further modify associations between serum folate concentrations and the risk of ESCC, but it was not significantly associated with the risk of EPL.
文摘Objective To investigate the association between the methylenetetrahydrofolate reductase gene C677T(MTHFR C677T)polymorphism and diabetic retinopathy(DR).Methods A total of 6971 subjects including 2707 DR patients and 4264 controls from 23 studies were enrolled in the study.A random-effects model was applied to estimate the overall effects and the stratified effects of the MTHFR C677T polymorphism on the risk of DR,and study quality was also assessed.Results Strong associations were observed between the MTHFR C677T polymorphism and DR.The carries of MTHFR C677T were more likely to be found in the DR group in relative to the healthy control group with odds ratio 1.6&2.55,and 2.31 respectively in allele contrast model(T vs.C,95%CZ:1.29-2.18,P<0.001,f=7&4%),homozygous model(TT vs.CC,95%CZ:1.70-3.83,P=0.008,72=54.4%)and dominant model(TT+CT vs.CC,95%CZ:1.62-3.29,P<0.001,12=74.7%).This association can also be found in contrast to the Ned(non-complicated diabetic mellitus)group(allele contrast,OR—1.50,95%Ch 1.07-2.11,P=0.032,I2=62.1%;homozygous,OR—2.39,9S%CZ:1.06-5.38,P=0.017,Z2=66.7%;dominant,OR=1.59,95%CZ:0.97-2.62,P=0.056,I2=56.5%).For the heterozygous model(CT vs.CC),the association was significant in contrast to the healthy control group(OR=1.46,95%CZ:1.64-3.69,P=0,P=77.3%),while in contrast to the Ned control group the association was not statistically meaningful(OR=1.38,95%CZ:0.87-2.18,P=0.131,Z2=43.7%).For the recessive model,1.92-fold increased risk was found only in contrast to the Ned control group(95%C1:1.07-3.43,P=0.064,P=55.0%).There was no significant association found in the models in contrast to the DM control group.Conclusion In this meta-analysis,we found an association between the MTHFR C677T polymorphism and DR,especially in contrast to the Ned control group.Further studies are required to establish more definite relationship.
文摘Objective: Migraine, a common chronic neurological disorder involves a pathophysiology having both multiple genetic and environmental factors. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) involved in folate metabolism has an important role in a cell for folate availability which is critical for DNA integrity. Methods: This case-control study conducted in Srinagar, Kashmir (North India) between 2013 and 2015 was designed to evaluate risk induced due to MTH-FR 677C>T gene polymorphisms to contribute in susceptibility for migraine in Kashmir population (North India). Using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, we tested the genotype distribution of 100 migraine patients in comparison with 120 healthy migraine-free controls from the same geographical region. Results: The genotypic frequencies of the patients and controls were not significantly associated (p > 0.05). Higher distribution of TT mutant genotype was found in controls as against the cases (5% versus 1%) but association was not significant (p > 0.05). Per copy frequency of T allele (Val) was found to be 0.14 in cases versus 0.19 in controls (p 0.05). Similar scenario was observed when migraine without aura was compared with controls where variant genotype (16% cases versus 39.0% controls: p > 0.05) as well as allele frequency was found to be less in cases (cases 0.15 versus 0.19 controls: p > 0.05). Conclusions: We conclude that MTHFR gene C677T polymorphism has no role in predisposition to the migraine in our population and cannot serve as a predictive factor for the risk of migraine.
文摘Alzheimer’s disease (AD) is a genetically complex and heterogeneous disorder. Although the clinical manifestations and the pathological features have been well elucidated, a clear etiology of AD is still unknown to this day. In the past few decades, investigations have elucidated that both the genetic and the environmental factors are capable of causing the development of AD. We report a patient with clinically diagnosed earlyonset Alzheimer's disease, age of onset 45 years. Genetic analysis revealed two MTHFR heterozygous polymorphisms C677T and A1298C.
