Association of Serum Adipsin Level with Insulin Resistance and Inflammatory Markers in Newly Diagnosed Type two Diabetes Mellitus Patients.

Adipsin is an anti-inflammatory adipokines and its altered level was seen in obesity and type II DM. Our study investigated the clinical significance of serum adipsin levels as a risk marker for type 2 diabetes and its relationships with insulin resistance and various adipo-cytokines. The study included 110 treatment-naïve T2DM cases and 100 controls of similar age and gender from northern India. Clinical, biochemical, and anthropometric characteristics were all profiled. Serum adipo-cytokines were measured using ELISA methods. Adipsin was significantly inversely correlated with body mass index (BMI), waist circumference, fasting plasma glucose, glycated haemoglobin (HbA1C), total cholesterol (TC), triglyceride (TG), homeostasis model assessment-estimated insulin resistance (HOMA-IR), tumour necrosis factor- α (TNF-α) and interleulin-6 (IL-6) and positively correlated with high-density lipoprotein cholesterol (HDL-C) and homeostasis model assessment of ß-cell function (HOMA-B) (P < 0.05). T2DM occurrence decreased with increasing concentration of adipsin with an odds ratio (OR) of 0.68 (95% CI = 0.58-0.79), P < 0.001. The area under curve (95% CI) for adipsin was 0.70 (0.63 to 0.76) with P < 0.001. The best cutoff value for adipsin to predict T2DM was < 5.50 µg/ml with 47.27% sensitivity and 82.00% specificity. FPG and WC were both independent predictors of serum adipsin levels. Our findings showed that high adipsin levels reduced the likelihood of T2DM and emerged as a potential risk marker in the prediction of T2DM.

Assesement of serum Sfrp5/Wnt-5a level and its utility in the risk stratification of treatment naïve patients with metabolic syndrome.

Our study focused on investigating the clinical significance of serum Sfrp5/Wnt-5a levels as a risk marker in metabolic syndrome (MetS). The study involved a total of 107 treatment-naive MetS cases and 100 controls with similar age and sex belonging to northern India. The profiling of clinical, biochemical, and anthropometric variables was done. ELISA methods were employed for serum cytokine estimation. Serum Sfrp5 was inversely correlated with BMI, WC, SBP, DBP, FPG, TG, fasting insulin level, and HOMA-IR in both males and females. The best cutoff value for Sfrp5 to predict MetS in males was ≤40.48 ng/ml (sensitivity 53.70% and specificity 90.48%), while in female, it was ≤66.67 ng/ml (sensitivity 98.11% and specificity 34.48%). MetS occurrence decreased with increasing concentration of Sfrp5 with an odds ratio (OR) of 0.95 (95% CI = 0.92-0.98, P < .001) in male and 0.93 (95% CI = 0.91-0.97, P < .001) in female. Quartile analysis revealed that odds of MetS significantly decreased in quartile 4 vs. 1, 0.06 (95% CI = 0.01-0.25), P = .001 and 0.13 (95% CI = 0.04-0.44), P = .001, respectively, in male and female. The inverse association of serum concentration of Sfrp5 with MetS might have a useful addition to the available risk marker as well as a therapeutic target for MetS.

No Association Between a Genetic Variant of FOXO3 and Risk of Type 2 Diabetes Mellitus in the Elderly Population of North India.

Aging can be considered an evolutionary process that is modulated by various genetic and biochemical processes. Therefore the genetic variants may interplay a role in human longevity as well as age related illness. Forkhead Box O (FOXO) gene is one of the major defensive genes that are known for ameliorating lifespan. FOXO proteins act as nuclear transcription factors that facilitate the action of insulin or insulin-like growth factor (IGF-1) in various physiological processes. The rationale of our study is to find out association between genetic variant rs2253310 of FOXO3 and risk of Type 2 Diabetes Mellitus (T2DM) in elderly population. This case control study involved 172 age sex matched elderly subjects while patients were recruited as per IDF criteria. Clinical, biochemical, ELISA methods were employed for assesement of clinical samples while Taqman method was used for genotyping analysis. Our results revealed that there was no significant difference in genotypic and allelic frequencies for the tested SNP (p > 0.05) between elderly T2DM patients and controls. The SNP rs2253310 was not associated with risk of T2DM in any genetic model. Also no association was found among the studied group between FOXO3 variant and HOMA-IR, HOMA-B index and Fasting plasma glucose. Serum level of inflammatory markers like CRP and TNF-α was significantly higher in patients but its not associated with SNP rs2253310. Our study concluded that, this intronic longevity-associated variant rs2253310 in FOXO3 is not associated with type 2 diabetes in geriatric patients of northern India.

Anti-diabetic Effect of Emblica-officinalis (Amla) Against Arsenic Induced Metabolic Disorder in Mice.

Chronic exposure to arsenic through drinking water and occupational exposure has been found to be associated with the diabetic symptoms. Earlier, we reported that arsenic induced enhanced oxidative stress, inflammation, dislipidemia and hepatotoxicity in mice have been protected by treatment with Emblica officinalis (amla). The present study has therefore been focused to investigate the efficacy of amla in mitigation of arsenic induced hyperglycemia in mice. Arsenic exposure (3 mg/kg b.w./day for 30 days) in mice altered glucose homeostasis and significantly decreases hepatic glucose regulatory enzyme, glucokinase (43%), glucose-6 phosphate dehydrogenase (38%), malic enzyme (60%) and significantly increases the level of glucose-6 phosphates (65%), phosphoenolpyruvate carboxykinase (43%), lactate, (59%) Na+ (6.8%) Cl- (10.4%), anion gap (13.9%) and pancreatic (IL-1ß, TNF-α) inflammation markers (52%, 53%) as compared to controls. Arsenic exposure also significantly decreased serum insulin (44%) and c-peptide protein (38%) in mice as compared to controls. Co-administration of arsenic and amla (500 mg/kg b.w./day for 30 days) balanced blood sugar level, hepatic glucose regulatory enzyme (glucokinase, glucose-6 phosphate dehydrogenase, malic enzyme (68%, 37%, 45%) and significantly decreases glucose-6 phosphatase (25%), phosphoenolpyruvate carboxykinase (22%), blood ion concentration and also lactate, Na+, Cl- and anion gap (20%, 4.6%, 6.7%, 5.2%), pancreatic (IL-1ß, TNF-α) inflammation marker (21%, 24%) and significantly increased the serum insulin (57%) and c-peptide protein (31%) as compared to those treated with arsenic alone. Results of the present study suggests that the hypoglycemic and antioxidant property of amla could be responsible for its protective efficacy in arsenic induced hyperglycemia.

Assessment of drug prescribing pattern using world health organization indicators in a tertiary care teaching hospital.

This cross-sectional study was carried out to assess drug prescribing pattern at a tertiary care teaching medical institute. One thousand prescriptions were randomly collected and analyzed using the world health organization prescribing indicators. The average number of drugs per prescription was 2.91. The percentage of drugs prescribed by generic name, from the essential drug list (National) and as fixed dose combinations (FDCs) was 10.05%, 22.57%, and 49.22%, respectively. The total percentage of encounters with antibiotics, injectables, and FDCs was 19.70%, 2.20%, and 73.60%, respectively. The most common group of drug prescribed was gastrointestinal tract drugs (26.38%) followed by Vitamins and Minerals (23.12%), cardiovascular system drugs (11.56%) and antimicrobials (9.63%). The prescribing practices were not appropriate as they consist of polypharmacy, lesser prescription by generic name, and overprescription of FDCs. There is a need for improvement in the standards of prescribing patterns in many aspects.

Correlation of Serum and Salivary Cytokines Level With Clinical Parameters in Metabolic Syndrome With Periodontitis.

BACKGROUND: Metabolic Syndrome (MS) and chronic oral condition (periodontitis [PD]) are state of inflammation. The study was conducted to determine alterations in serum and salivary cytokines level in MS and/or chronic PD in the North Indian population. MATERIALS AND METHODS: This cross-sectional study carried out in northern part of India. The study subjects of similar ethnicity were recruited according to International Diabetes Federation (IDF) criteria for MS, while chronic PD was diagnosed on the basis of packet depth and clinical attachment level. ELISA method was employed to assess cytokine level. All subjects were divided in four groups Gr A (MS + PD), B (MS), C (PD), and a control Gr D. RESULTS: The serum and salivary tumor necrosis factor alpha (TNF-α) level in Gr A, B, and C was significantly higher than Gr D (P < 0.05). Serum interleukin-10 (IL-10) level in Gr A, B, and C was lower than Gr D (P < 0.05), but this difference was not significant between Gr C and Gr D. Serum IL-10 level in Gr A was significantly lower than Gr C (P < 0.05). Salivary IL-10 level was not significantly altered in any group. CONCLUSIONS: Proinflammatory marker TNF-α has correlation with clinical parameters in patients of MS having PD. The study suggests level of salivary TNF-α may be utilized as a surrogate marker of MS and PD.

Meta-analysis on the association of nucleotide excision repair gene XPD A751C variant and cancer susceptibility among Indian population.

Polymorphism A751C (A>C) in XPD gene has shown susceptibility to many cancers in Indian population; however the results of these studies are inconclusive. Thus, we performed this meta-analysis to estimate the association between XPD A751C polymorphism and overall cancer susceptibility. We quantitavely synthesized all published studies of the association between XPD A751C polymorphism and cancer risk. Pooled odds ratios (ORs) and 95 % CI were estimated for allele contrast, homozygous, heterozygous, dominant and recessive genetic model. A total of thirteen studies including 3,599 controls and 3,087 cancer cases were identified and analyzed. Overall significant results were observed for C allele carrier (C vs. A: p = 0.001; OR 1.372, 95 % CI 1.172-1.605) variant homozygous (CC vs. AA: p = 0.001; OR 1.691, 95 % CI 1.280-2.233) and heterozygous (AC vs. AA: p = 0.001; OR 1.453, 95 % CI 1.215-1.737) genotypes. Similarly dominant (CC+AC vs. AA: p = 0.001; OR 1.512, 95 % CI 1.244-1.839) and recessive (CC vs. AA+AC: p = 0.001; OR 1.429, 95 % CI 1.151-1.774) genetic models also demonstrated risk of developing cancer. This meta-analysis suggested that XPD A751C polymorphism likely contribute to cancer susceptibility in Indian population. Further studies about gene-gene and gene-environment interactions are required.

Efficacy of crude extract of Emblica officinalis (amla) in arsenic-induced oxidative damage and apoptosis in splenocytes of mice.

INTRODUCTION: Arsenic, an environmental contaminant naturally occurred in groundwater and has been found to be associated with immune-related health problems in humans. OBJECTIVE: In view of increasing risk of arsenic exposure due to occupational and non-occupational settings, the present study has been focused to investigate the protective efficacy of amla against arsenic-induced spleenomegaly in mice. RESULTS: Arsenic exposures (3 mg/kg body weight p.o for 30 days) in mice caused an increase production of ROS (76%), lipid peroxidation (84%) and decrease in the levels of superoxide dismutase (53%) and catalase (54%) in spleen as compared to controls. Arsenic exposure to mice also caused a significant increase in caspases-3 activity (2.8 fold) and decreases cell viability (44%), mitochondrial membrane potential (47%) linked with apoptosis assessed by the cell cycle analysis (subG1-28.72%) and annexin V/PI binding in spleen as compared to controls. Simultaneous treatment of arsenic and amla (500 mg/kg body weight p.o for 30 days) in mice decreased the levels of lipid peroxidation (33%), ROS production (24%), activity of caspase-3 (1.4 fold), apoptosis (subG1 12.72%) and increased cell viability (63%), levels superoxide dismutase (80%), catalase (77%) and mitochondrial membrane potential (66%) as compared to mice treated with arsenic alone. CONCLUSIONS: Results of the present study indicate that the effect of arsenic is mainly due to the depletion of glutathione in liver associated with enhanced oxidative stress that has been found to be protected following simultaneous treatment of arsenic and amla.

Significance of impaired serum gelatinases activities in metabolic syndrome.

INTRODUCTION: A consortium of metabolic risk factors accelerate the onset of diabetes, heart disease, stroke, and certain cancers. Proteolytic enzymes like matrix metalloproteinases (MMP) are regulated by a group of endogenous proteins called tissue inhibitors of metalloproteinases (TIMP). These TIMPs binds to active and alternate sites of activated MMPs and facilitate regulation. Impaired expression of MMPs may have a significant contribution in the pathogenesis of many tissues-destructive processes like tumor progression and cardiovascular and metabolic disorders. MATERIALS AND METHODS: This case control study lays stress on the possible role of impaired levels of circulating MMP-2 and 9 in metabolic syndrome (MetS). The age, sex-matched 388 subjects with 190 newly diagnosed patients, and 198 healthy controls were recruited. To screen the patients with MetS, biochemical analysis of patients for impaired glucose level, hypertension, body mass index (BMI), and lipid profile was performed. The circulating level of MMP-2 and -9 in serum was analyzed by enzyme-linked immunosorbent assay (ELISA) in all patients and control. RESULTS: All metabolic risk factors were statistically significant (P < 0.01) in patients against control group. The serum MMP-2 and -9 level was significantly higher (P < 0.001) in patients having MetS as compared with control group. CONCLUSIONS: Similar trend was observed in gender wise analysis of serum MMP level. Higher MMP level alteration observed in male patients as compared with female patients.

Targeting self-care adherence for glycaemic control in multimorbid type 2 diabetes mellitus with depression using bupropion: a protocol for cross-over randomised controlled trial.

INTRODUCTION: Diabetes and depression are among the 10 biggest health burdens globally. They often coexist and exhibit a strong bidirectional relationship. Depression leads to decreased adherence to self-care activities. This impacts glycaemic control and worsens type 2 diabetes mellitus (T2D). Both conditions have a synergistic effect and lead to greater complications, hospitalisations, healthcare expenditure and a worse quality of life. There is no consensus on managing people with comorbid T2D and depression. Bupropion is an efficacious antidepressant with many properties suitable for T2D with depression, including a favourable metabolic profile, persistent weight loss and improvement in sexual dysfunction. We will assess the efficacy and safety of add-on bupropion compared with standard care in people with T2D and mild depression. This study can give valuable insights into managing the multimorbidity of T2D and depression. This can help mitigate the health, social and economic burden of both these diseases. RESEARCH DESIGN AND METHODS: This cross-over randomised controlled trial will recruit people with T2D (for 5 years or more) with mild depression. They will be randomised to add-on bupropion and standard care. After 3 months of treatment, there will be a washout period of 1 month (without add-on bupropion while standard treatment will continue). Following this, the two arms will be swapped. Participants will be assessed for glycosylated haemoglobin, adherence to diabetes self-care activities, lipid profile, urine albumin-to-creatinine ratio, autonomic function, sexual function, quality of life and adverse events. ETHICS AND DISSEMINATION: The Institutional Ethics Committee at All India Institute of Medical Sciences, Jodhpur has approved this study (AIIMS/IEC/2022/4172, 19 September 2022). We plan to disseminate the research findings via closed group discussions at the site of study, scientific conferences, peer-reviewed published manuscripts and social media. TRIAL REGISTRATION NUMBER: CTRI/2022/10/046411.

Apremilast Add-On Benefits Over Conventional Drugs (ABCD) in Unstable Non-segmental Vitiligo: A 12-Week Single-Center Randomized Controlled Trial.

Background Apremilast is an oral phosphodiesterase-4 enzyme inhibitor that modulates the immune system by increasing intracellular cyclic adenosine monophosphate levels and inhibiting inflammatory cytokines synthesis. We aimed to compare the efficacy and safety of add-on apremilast in combination therapy with standard treatment in patients with unstable, non-segmental vitiligo. Methods The study was a 12-week randomized, controlled, parallel-group, open-labeled trial. The control group received standard treatment (n=15), and the intervention group received 30 mg apremilast twice daily in addition to standard treatment (n= 16). Time to the first sign of re-pigmentation, halt in progression, and change in vitiligo area scoring index (VASI) score is the primary outcomes. Normality was assessed, and appropriate parametric and nonparametric tests were undertaken. Results Thirty-seven participants were randomized into two groups, and analysis was done on thirty-one participants. Over the treatment duration of 12 weeks, the median time to observe the first sign of re-pigmentation was four weeks in the add-on apremilast group compared to seven weeks in the control group (p=0.018). The halt in progression was observed more in the add-on Apremilast group (93.75%) compared to the control group (66.66%) (p=0.08). The VASI score decreased by 1.24 in the add-on apremilast group and 0.05 in the control group (p= 0.754). Parameters including body surface area, dermatology life quality index, and body mass index reduced significantly, while the visual analog scale increased significantly in the add-on apremilast group. However, results were comparable between groups. Conclusions Treatment with add-on apremilast accelerated clinical improvement. It also reduced disease progression and improved the disease index among participants. However, add-on apremilast had a lower tolerability profile than the control group.

Evaluation of the Effect of FOXO3 rs13217795 Genotype and Minor Allele (C) on Clinical Chemistry and Genetic Risk of Diabetes Among the Elderly Individuals from Northern India.

The forkhead box O family (FOXO) is expressed ubiquitously in a spatio-temporal manner and plays a key role in cellular metabolism, senescence, and aging. Genetic mutations in FOXO lead to metabolic diseases and cancer, and affect the longevity of individuals. Our study investigated how the genetic risk of type 2 diabetes mellitus (T2DM) altered due to an intronic variant rs13217795 of the longevity-associated FOXO3 gene in the geriatric population of North India. Genotypic characteristics of rs13217795 were determined among 347 age sex-matched (177 diabetic cases, 170 healthy controls) elderly individuals by TaqMan SNP assays after clinical assessment. Clinical chemistry and circulating cytokines level were assessed by biochemical and immunoassays. Genotype frequencies were not significantly (p = 0.526) different between cases and controls. The minor allele (C) frequency in diabetic cases and controls was 0.47 and 0.49, respectively (OR = 0.94, 95% CI = 0.69-1.26, p > 0.05). The minor allele was associated with lower fasting plasma glucose (FPG), fasting insulin, HOMA-IR, CRP, TNF-α, and IL-6 (p < 0.05). The homozygous minor allele carriers showed significantly lower levels of FPG, HOMA-IR, and TNF-α in T2DM patients. The minor allele (C) of intronic polymorphism in FOXO3 (rs13217795: T/C) confers the protective role characterized by its association with a decrease in glycemic and insulin resistance and proinflammatory markers.

SNPs of FOXO1 and Their Interactions Contributes to the Enhanced Risk of Diabetes Among Elderly Individuals.

We have assessed the impact of three single nucleotide polymorphisms (SNPs) of Forkhead Box O1 (FOXO1) and their interaction on susceptibility of type 2 diabetes mellitus in geriatric population from northern India. We genotyped three SNPs (rs2721068, rs17446614, and rs4581585) of FOXO1 gene in 190 elderly individuals with diabetes and 182 unrelated healthy controls of similar ethnicity by using TaqMan SNP assays. SNP-SNP and SNP-environment interactions among polymorphic loci were studied by the multifactor dimensionality reduction (MDR) method. The AA genotype carriers of rs17446614 was associated with the increased susceptibility of diabetes in both adjusted and unadjusted model, whereas rs4581585 was associated with the risk in unadjusted model only. Genotype and minor allele interaction with quantitative parameters revealed that AA genotype of rs17446614 had significantly higher fasting plasma glucose (FPG) in diabetic subjects, also minor allele (A) in patients was positively associated with FPG and glycated hemoglobin. Haplotype Trs2721068Grs17446614Trs4581585 increases the risk of diabetes, whereas carrier of haplotypes Crs2721068Grs17446614Crs4581585 and Crs2721068 Grs17446614Trs4581585 were protective. The MDR analysis revealed that interaction of rs17446614 with body mass index (BMI) increased the susceptibility of diabetes. Therefore presence of rs17446614 variant and its interaction with BMI and haplotype Trs2721068Grs17446614Trs4581585 modulates the risk of diabetes and can be used as a promising tool for identifying high-risk individuals.

Traditional knowledge to clinical trials: A review on therapeutic actions of Emblica officinalis.

Plants are the integral part of the traditional indigenous healthcare system and are becoming concrete source of new drug discovery, evident by the increasing numbers of modern drugs derived from the phytochemicals. Emblica officinalis Gaertn. or Phyllanthus emblica Linn (family Phyllanthaceae) has been explained extensively and well documented for its therapeutic efficacies in indigenous system of medicine, in India. Every part of this plant possesses high medicinal value but fruits are the most valuable part in folklore and therapeutic uses. The polyphenols found in E.officinalis, especially tannins and flavonoids are key responsible elements for major bioactivities. E.officinalis is one of the major component in various health tonics, also exerts synergistic effects in enhancing the medicinal efficacy. E.officinalis exhibits broad spectrum of pharmacological activities through various mode of actions including antioxidant, anticancer, immunomodulator, anti-inflammatory, cyto-protective properties etc. Medical practitioners across the globe also advocated its application in managing diabetes, dyslipidemia, obesity, several types of cancer, liver disorders, arthritis, gingivitis, wound healing etc. The present review analysed and summarized the pharmacological actions, experimental studies and clinical trials of E. officinalis with emphasis on its immuno-enhancer, antiinflammatory and anticancer activities and possible mechanism of actions to provide future directions in translating these findings clinically.

Comparative Effect of Insulin Sensitizers and Statin on Metabolic Profile and Ultrasonographical Score in Non Alcoholic Fatty Liver Disease.

INTRODUCTION: Non Alcoholic Fatty Liver Disease (NAFLD) is a metabolic disorder involving fat accumulation in the liver. The initial management for patients with NAFLD includes lifestyle modification and weight loss in overweight or obese patients. AIM: The present study was conducted to compare the efficacy of insulin sensitizers and statin in the patients of NAFLD. MATERIALS AND METHODS: The study included 98 patients diagnosed with NAFLD on USG (Ultrasonography) abdomen, divided into three Groups randomly and administered Metformin (Group I), Rosuvastatin (Group II) or Pioglitazone (Group III) along with dietary intervention and lifestyle modification. Their Body Mass Index (BMI), liver function tests, fasting lipid profile, USG scores for fatty liver were done and followed up at 4 weeks, 12 weeks and 24 week for change in above parameters. RESULTS: Out of the three Groups, Group II showed a maximum improvements in usg scores for NAFLD (p<0.001) and fasting lipid profile. Group II also showed maximum derangement of liver enzymes at 24 weeks though none of the subjects had more than three times elevation of liver enzymes. CONCLUSION: Rosuvastatin may be an effective therapy as add on treatment to dietary and lifestyle intervention in patients of NAFLD. As an add-on treatment Rosuvastatin was superior to Pioglitazone or Metformin and acute decompensation is unlikely with this drug. Metformin was not effective as add on therapy for NAFLD, rather rapid weight loss in short period of time resulted in worsening of hepatic steatosis.

Protective effect of Emblica-officinalis in arsenic induced biochemical alteration and inflammation in mice.

Exposure to arsenic in individuals has been found to be associated with immune related problems. In earlier studies, we have demonstrated that amla protects against arsenic induced oxidative stress and apoptosis in thymus and spleen of mice. In continuation to that the present study has therefore been focused to investigate the protective efficacy of amla in arsenic induced inflammation and immunotoxicity in mice. The results showed that arsenic treatment significantly increased serum urea levels (69 %), glucose levels (48 %) and triglyceride levels (66 %) as compared to controls. Mice exposed to arsenic exhibited significant increased in TNF-α (4.3-fold), serum Interleukin-1 beta (threefold), Interleukin-6 (3.8-fold) as compared to controls. Arsenic exposure increased the relative frequency of CD8+ (Tc) cells sub-population (18.9 %) and decreased CD4+ (Th) cells (2.6 %). Arsenic exposure also significantly decreased T (CD3) and B (CD19) cells (21.1 %) as compared to controls. Simultaneously treatment with arsenic and amla significantly inhibited serum urea levels (47 %), glucose levels (50 %) and triglyceride levels (14 %). It also significantly decreased the TNF-α (1.1-fold), levels of IL-1ß (1.6-fold), levels of Interleukin-6 (1.3-fold) in serum as compared to those treated with arsenic alone. Simultaneously treatment with arsenic and amla restored the alterations in CD8+ and CD4+ cells and also recovered the damages in B and T sub cells population. Results of the present study clearly indicate that arsenic induced immunotoxicity linked with inflammation has been significantly protected through simultaneous treatment with arsenic and amla that was due to anti-inflammatory and antioxidant activity of amla.

Genetic variants of matrix metalloproteinase (MMP2) gene influence metabolic syndrome susceptibility.

AIM: Matrix metalloproteinases (MMPs) are suggested to be involved in the development of various clinical factors of metabolic syndrome (MetS). Allelic variants in the promoter region of the MMP2 gene may modulate an individual's susceptibility to MetS. We performed this study to determine whether single-nucleotide polymorphisms (SNPs) -1575 (G>A) and -168 (G>T) of the MMP2 gene are associated with MetS risk. METHODS: In this hospital-based case-control study, 180 confirmed MetS patients and 190 unrelated healthy controls of similar ethnicity were genotyped for MMP2 (-1575 G>A, -168 G>T) polymorphisms using polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Variant genotype (AA) of -1575 showed increased risk (odds ratio [OR]=2.72, 95% confidence intervals [CI]=1.19-6.23, p=0.018) of MetS as compared to the wild-type homozygous genotype (GG). Similarly, the variant allele (A) (OR=1.60, 95%CI=1.12-2.26, p=0.009) and combined genotype (GA+AA) (OR=1.51, 95%CI=0.98-2.31, p=0.057) were also significantly associated with MetS risk. High risk of MetS was observed with respect to the haplotype (A-T) (OR=1.83, 95%CI=1.03-3.26, p=0.038) of MMP2 (-1575 and -168) polymorphisms. However, MMP2 (-168 G>T) polymorphism individually did not show any risk with MetS. CONCLUSIONS: Our results strongly support the notion that common sequence variants and haplotype of MMP2 (-1575 G>A and -168 G>T) might be a genetic risk for the development of MetS in the North Indian population. Additional studies on larger populations are needed to clarify the role of genetic variants of this gene in MetS.

Vascular endothelial growth factor 936 c>T polymorphism increased oral cancer risk: evidence from a meta-analysis.

AIM: The vascular endothelial growth factor (VEGF) plays a major role in angiogenesis. The association between VEGF 936 C>T (rs3025039) gene polymorphisms and oral cancer (OC) risk is still contentious and ambiguous. To assess the relationship between the VEGF 936 C>T genotype and the risk of developing OC, we performed a meta-analysis to summarize the possible association. METHODOLOGY: We assessed published studies of the association between 936 C>T polymorphisms and OC risk from four studies with 440 controls and 556 OC cases. We calculated pooled odds ratios (ORs) and 95% confidence interval (CI), considering the frequency of allele, homozygous, heterozygous genotypes and comparison of dominant and recessive genetic models. RESULTS: The combined results showed that the T allele was significantly associated with increased OC risk (T vs. C: p=0.001; OR=1.521, 95% CI=1.194-1.938). The heterozygous genotype CT had a 1.5-fold increased risk (CT vs. CC: p=0.002; OR=1.582, 95% CI=1.184-2.114). In addition the dominant genetic model demonstrated a 1.6-fold increased risk of developing OC (TT+CT vs. CC: p=0.001; OR=1.621, 95% CI=1.226-2.143). CONCLUSION: Our results suggest that the VEGF gene polymorphism (936 C>T) contributes increased susceptibility to OC. However, larger studies with a stratified case-control population and biological characterization are needed to validate this finding.