Association between polymorphisms in human tumor necrosis factor-alpha (−308) and -beta (252) genes and development of gestational diabetes mellitus (original) (raw)
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Study of inflammatory markers and TNF-? g308a and gene polymorphism in gestational diabetes mellitus
International Journal of Clinical Biochemistry and Research
Introduction: The prevalence of Gestational diabetes mellitus (GDM) is increasing world wide. It has been said that plasma levels of TNF-α is regulated by single nucleotide polymorphism in promoter region of TNF-α gene in development of GDM. The study was done to determine Tumor Necrosis Factor-α (TNF) levels and its gene Polymorphism in GDM cases and controls and to correlate them with each other. Materials and Methods: A total of 60 patients were selected comprising 30 diagnosed GDM cases and 30 apparently healthy pregnant women from ANC matched for age and gestation. OGTT was conducted and glucose estimated by GOD-POD method (Beckman AU-480 auto-analyzer) and serum TNF-α levels using sandwich ELISA. TNF-α 308(G/A) gene polymorphism was analyzed by extracting DNA from whole blood (using QIAGEN DNA mini kit) followed by DNA amplification by PCR and RFLP using restriction enzyme Nco1. Results: TNF-α levels were significantly increased in GDM cases (28.93±20.96 pg/ml) as compared to controls (19.4±11.6 pg/ml). TNF-α polymorphism revealed GG genotype in 87% cases and 93% controls; AA 3% of cases and 7% of controls and GA 10% of cases and absent in controls. However, the difference was statistically insignificant. TNF-α levels did not significantly correlate with the polymorphism. ROC analysis showed area under the curve of 0.613 for prediction of GDM. Conclusion: In GDM significant increase of TNF-α levels signifies the role of inflammation in the etio-pathogenesis. The TNF-α G308A gene Polymorphism in particular is however not significantly associated with GDM.
TNF-α Gene G308A Polymorphism: Frequency in Patients with Type 2 Diabetes Mellitus
International Journal of Current Research and Review
Introduction: Tumour necrosis factor-alpha (TNF-α), a pro-inflammation cytokine, plays a critical role in the pathogenesis of type 2 diabetes mellitus due to involving into the regulation of insulin signalling. Overproduction of this cytokine in metabolic syndrome is linked to TNF-α promoter gene G-308A polymorphism. Objective: The work was initiated to measure the serum TNF-α concentrations and to determine the frequency of the Tumour necrosis factor-alpha (TNF-α) gene G308A polymorphism in Uzbek patients with type 2 diabetes mellitus. Methods: Healthy and type 2 diabetes mellitus Uzbek patients were observed. Results: In the group with diabetes fasting blood glucose and the glycated haemoglobin (HbA1c) levels were 2.7 and 1.6 times higher respectively (both p<0.01). HDL cholesterol was reduced, while LDL cholesterol, total cholesterol and triglycerides were higher in diabetic group. There was a significant difference between the serum TNF-α concentration in people with and without DM. As to TNF-α gene G308A polymorphism in the sample under study, it was represented mostly by GG homozygous genotype to be registered among persons without diabetes (90.2%) and patients with type 2 DM (83.3%). GA heterozygous genotype occurred in 9.8% and 16.7% of non-diabetics and diabetics, respectively. In our study, pathological AA homozygous genotype was found neither among the diabetics nor in the controls. There were no significant differences in frequencies of alleles and genotypes of TNFα gene G308A polymorphism. In the diabetics, frequencies of A allele and GA genotype is insignificantly higher than those in the controls. Conclusion: In compare to non-diabetic controls, patients with type 2 diabetes mellitus had higher serum concentrations of TNF-α. However, in that small group association of A allele and GA genotype of TNF-α gene with a higher risk of DM2 were insignificant.
Human Immunology, 2010
A case-control study was performed to establish a potential association of two TNF-␣ gene promoter SNPs (Ϫ238GϾA and Ϫ308GϾA) with occurrence of type 1 Diabetes mellitus (T1DM) in Croatian population (174 patients and 193 healthy controls). Genotypes (obtained by polymerase chain reaction-restriction fragment length polymorphism), and the clinical parameters of T1DM patients were statistically evaluated by SPSS 13 and Arlequin software, G*Power 3.0.10 program, and calculator for Hardy-Weinberg equilibrium. The frequency of the risk (A) allele, as well as the distribution of high-expression (GA, AA) genotypes were significantly higher (p Ͻ 0.0001) in T1DM patients only at locus Ϫ308. The distribution of the Ϫ238G/Ϫ308A haplotype was also significantly higher in patients compared with controls (27.6% vs 9.6%, p Ͻ 0.0001). Gender-dependent analysis revealed that female T1DM Ϫ308GA genotype carriers exhibit considerably stronger association with T1DM (odds ratio ϭ 6.37, 95% confidence interval ϭ 3.16 -12.85) than male Ϫ308GA patients (odds ratio ϭ 2.71, 95% confidence interval ϭ 1.31-5.59). Clinical parameter analysis of T1DM patients revealed significantly decreased level of hemoglobin A 1 c (HbA 1 c) in Ϫ238A allele carriers compared with Ϫ238G allele carriers (6.55% vs 7.17%, p ϭ 0.022), as well as the tendency of the risk allele carriers at Ϫ238 or Ϫ308 locus to develop T1DM earlier in life compared with non-risk allele carriers. In conclusion, susceptibility to T1DM in the Croatian population is strongly associated with the TNF-␣ Ϫ308GϾA polymorphism, especially in women. In addition, significantly lower HbA 1c levels found in T1DM Ϫ238A allele carriers might indicate better glycemic control in these patients. ᭧
Clinical Biochemistry, 2012
We examined the possible association of the −308G/A polymorphism of the TNF-α promoter gene in type 2 diabetes mellitus (DM2) patients and in non-diabetic subjects with and without family history of DM2. Methods: We studied 87 non-diabetic subjects without DM2 family history in at least one of two generations, 48 non-diabetic subjects with DM2 family history and 95 DM2 patients. Genotyping was carried out by PCR-RFLP. Results: The frequency of TNF-α −308G/A genotype was significantly lower in non-diabetic subjects without DM2 relatives (6%) as compared to DM2 patients (24%) (odds ratio (OR)= 5.24; 95% confidence interval (CI) = 1.9-15.8, p b 0.0005), but similar to non-diabetic subjects with DM2 relatives (29%) (OR = 0.77; CI= 0.3-1.7, p = 0.4). Logistic regression analysis showed the association of TNF-α −308G/A polymorphism with DM2 family history (OR = 5.80; CI = 1.77-18.98, p b 0.0003). Conclusions: Our results suggest that TNF-α −308G/A polymorphism is associated with DM2 family history and is a risk factor for DM2.
Study of inflammatory markers and TNF-α g308a and gene polymorphism in gestational diabetes mellitus
IP innovative publication pvt. ltd, 2019
Abstract Introduction: The prevalence of Gestational diabetes mellitus (GDM) is increasing world wide. It has been said that plasma levels of TNF-α is regulated by single nucleotide polymorphism in promoter region of TNF-α gene in development of GDM. The study was done to determine Tumor Necrosis Factor-α (TNF) levels and its gene Polymorphism in GDM cases and controls and to correlate them with each other. Materials and Methods: A total of 60 patients were selected comprising 30 diagnosed GDM cases and 30 apparently healthy pregnant women from ANC matched for age and gestation. OGTT was conducted and glucose estimated by GOD-POD method (Beckman AU-480 auto-analyzer) and serum TNF-α levels using sandwich ELISA. TNF-α 308(G/A) gene polymorphism was analyzed by extracting DNA from whole blood (using QIAGEN DNA mini kit) followed by DNA amplification by PCR and RFLP using restriction enzyme Nco1. Results: TNF-α levels were significantly increased in GDM cases (28.93±20.96 pg/ml) as compared to controls (19.4±11.6 pg/ml). TNF-α polymorphism revealed GG genotype in 87% cases and 93% controls; AA 3% of cases and 7% of controls and GA 10% of cases and absent in controls. However, the difference was statistically insignificant. TNF-α levels did not significantly correlate with the polymorphism. ROC analysis showed area under the curve of 0.613 for prediction of GDM. Conclusion: In GDM significant increase of TNF- α levels signifies the role of inflammation in the etio-pathogenesis. The TNF-α G308A gene Polymorphism in particular is however not significantly associated with GDM. Keywords: Gestational diabetes mellitus, TNF-α G308A gene polymorphism.
Journal of Applied Biology & Biotechnology, 2019
This study was designed to inspect the association between tumor necrosis factor (TNF)-α-308G/A (rsl800629) polymorphism with diabetes mellitus type-2 (DMT2) in Bangladeshi population. Besides, the role of TNF-α-308G/A in early proliferation of DMT2 has been investigated. The allelic frequency of TNF-α-308G/A and their association with DMT2 was studied using high resolution melting (HRM) analysis and confirmed using sequencing. A few demographic risk factors associated with DMT2 were also investigated routinely. The significance of these risk factors was analyzed statistically. We have analyzed 657 individuals who were distributed into two groups: 330 non-diabetic controls and 327 DMT2 individuals. HRM analysis shows that 11 individuals bare G/A and 2 bare A/A genotype in DMT2 patients. Within non-diabetic individual, we found only one with G/A genotype. The frequency of TNF-α-308G>A are within the Hardy-Weinberg equilibrium (0.00482) at 95% confidence level. TNF-α-308G>A frequency in two age group based on first time diagnosed, we found association with early proliferation of DMT2 with a p-value of 0.008965 in Fisher's test at 95% confidence level. Our result suggested that the single nucleotide polymorphisms TNF-α-308G>A is closely associated with DMT2 patients in Bangladeshi population. Besides, presence of TNF-α-308G>A polymorphism increases the risk of early proliferation of DMT2.
Hereditas, 2010
Gestational diabetes mellitus (GDM), defi ned as carbohydrate intolerance diagnosed for the fi rst time during pregnancy, affects both maternal and fetal health. Possession of a specifi c genetic polymorphism can be a predisposing factor for susceptibility to some diseases. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNP) in the promoter gene of interleukin-10 (IL-10) as well as tumor necrosis factor-alpha (TNF α) with the development of GDM. Two hundred and twelve consecutive series of eligible normal pregnant women (controls) and gestational diabetes mellitus women were selected based on the study's inclusion and exclusion criteria. DNA was extracted from blood and genotyped for IL-10 at three positions and TNF α for gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of IL-10 and TNF α at different gestational periods as well as postpartum were quantifi ed using enzyme linked immunosorbent assay (ELISA). The results of the study showed that the difference in the frequency of SNP at position-597 in the promoter of the human IL-10 gene between the control and GDM groups was statistically signifi cant (p Ͻ 0.05). In contrast, there was no signifi cant difference in the frequency of SNP at the other two sites in the promoter region of the human IL-10 gene (-824 and-1082) as well as position-308 in the promoter of the human TNF-α (p Ͼ 0.05). In addition, there was no signifi cant difference between the two groups in terms of plasma levels of IL-10 as well as TNF α in different stages of pregnancy. SNP at position-597 was signifi cantly associated with the development of GDM and shows potential for use as a predictive marker for GDM.
Journal of Advanced Biotechnology and Experimental Therapeutics, 2021
ABSTRACT: Tumor necrosis factor-alpha (TNF-α) is a major cytokine for inflammatory response in human body. This is also well linked with obesity and causing different pathophysiological problems in type 2 diabetic mellitus (T2DM) patients because of its pro-inflammatory over expression. However, seemingly harmless nucleotide changes in the promoter region often cause oscillation in expression, results in complications like dyslipidemia and atherosclerosis that ultimately exploit to coronary heart disease (CHD). Therefore, this study was designed to evaluate association between TNF-α (-308G>A) polymorphism at promoter region and CHD in T2DM patients from the northern region (Rajshahi) of Bangladesh. The total number of participants was 96 T2DM patients. TNF-α polymorphism were detected using high resolution melting (HRM) curve analysis. A total of 32 participants were suffering from CHD and 8 polymorphism (3 homozygous and 5 heterozygous) were detected among them. From Fisher's Exact test, we found significant (P < 0.05) relationship between TNF-α (-308G>A) polymorphism and CHD in T2DM patients. According to Kendall's Tau correlation matrix (r = 0.218), there is a good correlation between target polymorphism and CHD. Therefore, the overall results suggest that TNF-α promoter (-308G>A) polymorphism influences CHD in T2DM patients.