Endothelial nitric oxide synthase (eNOS) VNTR as a probable marker in type 2 diabetes mellitus.

Background: The gene encoding eNOS is located on chromosome 7q36, a genetic region previously linked to metabolic syndrome, cardiovascular and renal diseases. Generally, in diabetes there are numerous genes involved, each being a small contributor in type 2 diabetes mellitus (T2DM) manifestation. A 27 bp variable number of tandem repeat (27 bp VNTR a/b) in intron 4 of enos gene has gained attention and this polymorphism may affect the expresssion of eNOS. We studied the association of eNOS-27 bp VNTR with T2DM in north indian population. Material and methods: Blood samples were collected in 0.5 M EDTA from 200 T2DM patients and 210 age/sex matched healthy controls. Genomic DNA was extracted from peripheral blood mononuclear cells (PBMCs) using the salting out method. The 27-VNTR polymorphism was determined by standard PCR amplification using forward and reverse primers 5'-AGGCCCTATGGTAGTGCCTTT-3’ and 5'-TCTCTTAGTGCTGTGGTCAC-3’ respectively. The genotypes were determined by analyzing the amplified products on 2% agarose gels. Genotypic and allelic frequencies were calculated by SPSS (version 15.0). Results: Clinical and biochemical profiles of healthy controls and T2DM cases as well as gender wise comparisons showed significant association in certain parameters (p<0.001). Five different alleles (I, II, IV, V and VI) were found in the study population. The genotypic frequency was significantly associated with T2DM (P <0.001). Conclusion: A significant role of allele ‘I’ in T2DM susceptibility was an interesting observation. Therefore, The 27 bp VNTR in eNOS gene polymorphism can be used as a probable marker in determining susceptibility to T2DM in north Indian population.

Interleukin-6 (IL-6)-597 A/G (rs1800797) & -174 G/C (rs1800795) gene polymorphisms in type 2 diabetes.

Background & objectives: Diabetes is a metabolic pro-inflammatory disorder characterized by chronic hyperglycaemia and increased levels of circulating cytokines suggesting a causal role for inflammation in its aetiology. In order to decipher the role of interleukin-6 (IL-6) in type 2 diabetes mellitus (T2DM) we analyzed two promoter polymorphisms -597 A/G (rs1800797) and -174 G/C (rs1800795) in T2DM cases from north India, and in healthy controls. methods: DNA was isolated from venous blood samples of T2DM patients (n=213) and normal healthy controls (n=145). Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed after biochemical analysis. The genotypic and allelic frequency distributions were analyzed. Results: The clinical/biochemical parameters of T2DM cases when compared to controls showed a significant difference. No significant association was observed with -597A/G polymorphism while, -174 G/C showed a highly significant association (P<0.001). In haplotypic analysis, combination of -597G*/-174C* showed significant association (P=0.010). Interpretation & conclusions: Our data suggest that IL-6 gene polymorphisms play a prominent role in T2DM disease susceptibility in population from north India.

Association of apolipoprotein B XbaI gene polymorphism and lipid profile in northern Indian obese.

BACKGROUND: Over the last few decades, obesity, diabetes, and hypertension have become main health evils. The health problems of obesity are well-recognized. However, the fact that all obese individuals are not at the same risk of developing a disease is also recognized. The apolipoprotein B (APOB) plays a central role in lipid metabolism. So we compare the association of APOB XbaI gene polymorphism and lipid profile total in obese north Indian population. MATERIALS AND METHODS: A total of 132 obese (body mass index [BMI] >25 kg/m2) and 132 age matched non-obese (BMI ≤ 25 kg/m2) subjects were studied after taking detailed clinical profile. Lipid profile in serum/plasma was done using commercial kits. Genetic analysis of APOB XbaI was done using Polymerase Chain Reaction-Restriction Fragment Leanth polymorphism (PCR-RFLP). STATISTICAL ANALYSIS: Statistical analysis was performed by Statistical Package for the Social Sciences (SPSS) (version 11.5) software (IBM Corporation). All continuous variables were expressed as mean ± SD and tested by analysis of variance test. Comparisons of categorical variables were assessed using χ2 tests or Fisher's exact test. P < 0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of the waist-to-hip ratio, blood pressure (systolic and diastolic), and lipid profile. In APOB XbaI gene polymorphism, we did not find significant differences in genotype or allele frequencies. Moreover, none of the studied metabolic parameters (lipid profile) showed any association with the gene polymorphism. CONCLUSIONS: Study reveals no considerable association of APOB XbaI gene polymorphism with obesity and lipid profile in north Indians.

Effect of yoga nidra on physiological variables in patients of menstrual disturbances of reproductive age group.

Aim of this study was to see any effect on autonomic functions in menstrual disturbances patients after Yoga Nidra practice. The subjects for the study were 150 females with menstrual irregularities, 28.08±7.43 years of mean age, referred from department of Obstetrics and Gynecology CSMMU, UP, Lucknow. Subjects were divided randomly in to two groups’ intervention and in control groups -seventy five (75) in each group. Out of these, one hundred twenty six (126) completed the study protocol. The yogic intervention consisted of 35-40 minutes/day, five days in a week till six months. An autonomic function testing was done in both the groups at zero time and after six months. A significant positive effect was observed when yoga therapy was used as an adjunct in the patients of menstrual disturbances. There were significant improvements in the blood pressure, postural hypotension and sustained hand grip, heart rate expiration inspiration ratio and 30:15 beat ratios of the subjects after yogic practice.

Association of β2-adrenergic receptor and insulin receptor substrate-1 polymorphisms with obesity in a Northern Indian population.

BACKGROUND: Imbalance in hormonal levels, regulated by host genetic factors, are known to be a major cause of obesity. Therefore, we aimed to evaluate association of genetic polymorphisms of β2-adrenergic receptor (β2-AR) and insulin receptor substrate-1 (IRS-1) with hormonal levels in northern Indian obese. METHODS: A total of 111 obese and 89 age matched non-obese subjects were studied after taking detailed clinical profile. Hormonal assays in serum/plasma for different hormones were done using IRMA and RIA kits. Genetic analysis of β2-AR (-47 and -20, T to C) and IRS-1 (Arg972Gly) was done using PCR-RFLP. STATISTICAL ANALYSIS: Statistical analysis was performed by SPSS (version 11.5) software. All continuous variables were expressed as mean ± SD and tested by ANOVA test. Comparisons of categorical variables were assessed using X2 tests or Fisher's exact test. P-value <0.05 was considered as significant. RESULTS: Analysis showed that obese subjects had significantly higher value of blood pressure (systolic), WHR, leptin insulin and glucagon and lower value of GH. In β2-AR (-47) T/C and IRS-1 Gly972Arg gene polymorphisms we did not found significant differences in genotype or allele frequencies. Moreover, none of the studied hormonal or metabolic parameters showed any association with the gene polymorphisms. CONCLUSIONS: Study reveals no significant association of β2-AR (-47 and -20, T to C) and IRS-1 Gly 972 Arg polymorphisms with obesity in northern Indians.

Pathophysiology and genetics of obesity.

Obesity, a global problem, is a multifactorial disorder. The factors are environmental, metabolic and genetic and their interaction with each other regulates the body weight. Imbalance in either of the factors may be responsible for weight gain. With advancement of research techniques in the last decade, genetic studies have been undertaken for several different causative mutations involving obesity loci on different chromosomes. Monogenic and polygenic obesity has been observed however, polygenic forms are more common. So far more than 200 genes in mouse and more than 100 genes in humans have been identified which result in phenotypes that affect body weight regulation. In spite of this knowledge, the field of obesity has still not been explored extensively. There remain a lot of lacuna regarding causes and treatment of obesity. Challenges are still there to identify the exact cause of weight gain and the use of current knowledge for development of anti-obesity drugs targeted for body weight regulation. In this review, we have explained neuropathophysiologic regulation of feeding behaviour and some aspects of obesity-genetics especially with single nucleotide polymorphism of selected candidate genes and their functional aspects mainly in monogenic obesity.