Metabolic syndrome and risk of major coronary events among the urban diabetic patients: North Indian Diabetes and Cardiovascular Disease Study-NIDCVD-2

Objective: The present study aimed at estimating the prevalence of metabolic syndrome (MetS) and prospectively, evaluating cardiovascular events among Asian Indians type 2 diabetic subjects. Methods: The sample comprised 1522 type 2 diabetic mellitus (T2DM) subjects aged 25-91. years, who participated in the North Indian Diabetes and Cardiovascular Disease Study (NIDCVD). The participants were screened for hypertension, dyslipidemia, obesity and cardiovascular events. Anthropometric, clinical and biochemical measurements were done in all subjects. The prevalence of MetS was estimated in all the subjects according to the harmonized criteria of 2009. Results: The prevalence of MetS among urban Indian diabetic subjects was 71.9% and was significantly higher in females (86%) as compared to males (57.9%). To determine the independent predictors of the MetS in diabetic sample, binary logistic regression analyses were performed using demographic and biochemical parameters. Significant differences in the indices of generalized and abdominal obesity and lipids (total cholesterol, high density lipoprotein) were observed (p <. 0.01) in male:female and MetS and non-MetS comparisons. Regression analysis for prediction of CAD showed that family history, age, body mass index (BMI), SBP, physical inactivity and hypertension independently and significantly predicted the disease outcome. Binary logistic regression analysis revealed that MetS may be an independent risk/predictor of CAD (odd ratio (OR) = 3.44, CI 1.31-9.01, p = 0.012) along with higher age groups, BMI and hypertension in Indian population. Conclusion: The study demonstrated that the high prevalence of MetS and its different components were positively associated with a higher risk of CAD in north Indian diabetic subjects. Nevertheless, MetS is a major health problem in India, comprehensive population studies are warranted for estimation of incidence and prevalence, and education should be provided on its prevention and control to reduce the diabetes-related morbidity and mortality

Prevalence and predictors of age related macular degeneration in the population of Punjab: North Indian age related macular degeneration epidemiology and molecular genetic study (NI-ARMEMS)

Background: Age related macular degeneration (AMD) is an ocular disease that is threatening elderly population of Punjab for vision impairment and blindness. Comprehensive understanding of the susceptible factors still remains to be explored in this region. Objective: To examine the risk variables which are independently associated with the risk of AMD along with the investigation of its prevalence in the population of Punjab. Methods: A case-control study by design involved 416 subjects (cases; 219, controls; 197) of age ranging from 45 to 75 years. Various risk factors were investigated for their role in consenting and confirmed AMD subjects along with controls. Results: In the univariate full factorial regression analysis, advancing age (≥66years), being a woman, diastolic blood pressure (DBP) (>80mmHg), cigarette smoking, alcohol drinking, body mass index (BMI) (23-29.9Kgm-2 and ≥30Kgm-2 ), sedentary life style, total cholesterol (>200mg/dl), low density lipoproteins (>100mg/dl), high density lipoproteins (≥40mg/dl), non-vegetarian diet and positive family history were found to be risky determinants. Multivariable stepwise regression analysis revealed age ≥66 years, DBP > 80mmHg, alcohol drinking and smoking as independent predictors for the risk of AMD. Conclusion: Considerable prevalence of dry AMD (20.5%) is evident in the population of Punjab which is mediated independently by age (≥66 years), DBP (>80 mmHg), alcohol drinking and smoking

Paraoxonase 1 gene polymorphisms (Q192R and L55M) are associated with coronary artery disease susceptibility in Asian Indians

Background: Coronary artery disease (CAD) is a complex metabolic disorder in which lifestyle and genetic factors are known to play key roles in pathogenesis. The paraoxonase 1 (PON1) enzyme has a defensive effect against CAD progression, as it safeguards low-density lipoproteins (LDLs) from oxidative modifications. The most extensively studied genetic variants in the PON1 gene are Q192R and L55M, which have been related with LDL antioxidative activity and risk of CAD. Objective: The present case-control study intended to examine the Q192R and L55M polymorphisms and their association with the risk of CAD patients in north Indians. Methods: A total of 872 subjects (412 CAD patients and 460 controls) were recruited from north India. The PON1 gene was amplified and genotypes were studies using PCR-RFLP. χ2 analysis was performed to compare genotype/allele frequencies in patients and controls. Results: The present study indicated abdominal obesity, elevated body mass index, and dyslipidemia with increased levels of total cholesterol and triglycerides as well as reduced high-density lipoprotein cholesterol in CAD subjects compared to healthy controls (p < 0.05). Logistic regression analysis of the data revealed an association of the RR genotype of the Q192R polymorphism with an about 2-fold elevated risk of CAD (OR = 2.23, 95% CI = 1.47–3.37, p = 0.0001). Contrariwise, the L55M polymorphism did not show significant association with CAD (OR = 1.81, 95% CI = 0.66–4.95, p = 0.326). Conclusions: The Q192R polymorphism in the PON1 gene may be a susceptibility gene associated with increased risk of CAD in an Asian Indian population

ENPP1 K121Q functional variant enhances susceptibility to insulin resistance and dyslipidemia with metabolic syndrome in Asian Indians

Background: Ectonucleotide pyrophosphatase/phosphodiesterase1 (ENPP1/PC-1) is a key modulator of the insulin signaling pathway, and its common variant, K121Q, increases the susceptibility to diabetes and cardiovascular diseases. Objectives: The main objective of the present study was to investigate the association of ENPP1 K121Q polymorphism with the pathophysiology of metabolic syndrome (MetS) in a north Indian population. Methods: A total of 567 participants (303 MetS subjects and 264 healthy controls) were examined for ENPP1 genotypes and various clinical parameters, including body mass index (BMI), waist circumference (WC), systolic and diastolic blood pressures (SBP/DBP), fasting blood glucose (FBG), cholesterol, triglycerides (TG), highdensity lipoprotein, and insulin. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Statistical analysis of the data was done using SPSS. Results: Significant increases in BMI, WC, SBP, DBP, FBG, TG, low-density lipoprotein, insulin, and Homeostasis Model Assessment of insulin resistance (HOMAIR) and of beta-cell function (HOMA-BF) were observed in MetS patients compared to healthy controls. Logistic regression analysis of data demonstrated a nonsignificant association of QQ and KQ+QQ genotypes with increased risk of MetS (OR [95% CI], 1.583 [0.455–5.507], p = 0.470 for QQ genotypes and 1.097 [0.784–1.540], p = 0.587 for KQ+QQ genotypes). Moreover, MetS subjects carrying Q alleles had significantly higher levels of TG, insulin, body fat percentage, and insulin resistance as evident by higher values of HOMAIR. Conclusions: We conclude that ENPP1 K121Q functional variant enhances susceptibility to insulin resistance and dyslipidemia in MetS subjects of an Asian Indian population

The role of TLR4, TNF-α and IL-1β in type 2 diabetes mellitus development within a North Indian Population.

This study investigated the role of IL-1β-511 (rs16944), TLR4-896 (rs4986790) and TNF-α-308 (rs1800629) polymorphisms in type 2 diabetes mellitus (T2DM) among an endogamous Northern Indian population. 414 participants (204 T2DM patients and 210 non-diabetic controls) were genotyped for IL-1β-511, TLR4-896 and TNF-α-308 loci. The C allele of IL-1β-511 was shown to increase T2DM susceptibility by 75% (OR: 1.75 [CI 1.32-2.33]). Having two parents affected by T2DM increased susceptibility by 5.7 times (OR: 5.693 [CI 1.431-22.648]). In this study, we have demonstrated a conclusive association with IL-1β-511 locus and IL1B-511-TLR4-896 diplotype (CC-AA) and T2DM, which warrants further comprehensive analyses in larger cohorts

Genetic variation and differentiation among a native British and five migrant South Asian populations of the East Midlands (UK) based on CODIS forensic STR loci

Background: Short Tandem Repeats (STRs) are widely used in population and forensic genetic studies.Aim: The objective of this study was to document the level and extent of genetic variation of the FBI Combined DNA Index System (CODIS) STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX and CSF1PO) in 6 populations (British, Indian (Punjabis and Gujaratis), Pakistani, Bangladeshi and Sri Lankan) of the East Midlands (UK). There is a lack of genetic research on the migrant South Asian populations.Subjects and methods: DNA samples (N = 603) were analysed for 13 autosomal forensic STR loci along with the amelogenin locus following standard protocols. Data were analysed for genetic variation and a range of forensic indices.Results: All loci were polymorphic in all populations with a variable degree of variation. Average observed heterozygosity was highest in Bangladeshi (0.803) and lowest in Punjabi (0.761). FGA locus had the highest power of discrimination (PD) in most populations.Conclusion: FGA locus was most polymorphic and discriminatory among migrant populations demonstrating it as the marker with the highest potential in forensic analyses. These results could be useful for population and forensic genomic studies.</div

Genomic diversity and differentiation of Alu insertion polymorphisms in a native British and four South Asian migrant populations

Background Alu insertions are bi-allelic and primate-specific, this makes them a useful marker for studying genetic variation, migration patterns, forensic analyses, paternity, and evolutionary heritage, however, specific population studies are limited. Aim The objective of this study is to document the level and extent of genetic variation at 39 different Alu loci in 5 populations (British, Indian Punjabi, Indian Gujarati, Pakistani, and Bangladeshi) from the East Midlands region of the UK. Genetic data on migrant populations is currently limited. Subjects and Methods DNA samples (N = 543) were analysed for 39 Alu insertion polymorphisms using specific primers and standard protocols. Data were analysed for population and forensic genetic parameters. Results All studied Alus were polymorphic in the British White population while South Asian migrant populations had a variable number of loci which were monomorphic. Highest heterozygosities and lowest match probabilities were observed in the British sample while the Bangladeshi sample had the lowest heterozygosity and higher match probability. Conclusion The analysed Alus insertions (TPA25, Ya5NBC123, Ya5NBC182, Ya5NBC241 and Ya5NBC242,) are highly polymorphic and variable among migrant populations. These loci could be useful for population genomic and differentiation studies.</p

Targeting mitochondrial bioenergetics as a promising therapeutic strategy in metabolic and neurodegenerative diseases

Mitochondria are the organelles that generate energy for the cells and act as biosynthetic and bioenergetic factories, vital for normal cell functioning and human health. Mitochondrial bioenergetics is considered an important measure to assess the pathogenesis of various diseases. Dysfunctional mitochondria affect or cause several conditions involving the most energy-intensive organs, including the brain, muscles, heart, and liver. This dysfunction may be attributed to an alteration in mitochondrial enzymes, increased oxidative stress, impairment of electron transport chain and oxidative phosphorylation, or mutations in mitochondrial DNA that leads to the pathophysiology of various pathological conditions, including neurological and metabolic disorders. The drugs or compounds targeting mitochondria are considered more effective and safer for treating these diseases. In this review, we make an effort to concise the available literature on mitochondrial bioenergetics in various conditions and the therapeutic potential of various drugs/compounds targeting mitochondrial bioenergetics in metabolic and neurodegenerative diseases.</p

Vitamin D receptor (VDR) gene polymorphism and osteoporosis risk in White British men

In this study, VDR gene ApaI (rs7975232), BsmI (rs 1544410) and TaqI (rs731236) genotypes were compared in men with osteoporosis and male controls. Osteoporosis affects around 20% of all men and overall mortality in the first year after hip fracture is significantly higher in men than women, yet the genetic basis of osteoporosis is less well studied in males. This study consisted of White British males; 69 osteoporosis patients and 122 controls. BMDs at the lumbar spine (vertebrae L1-L4) and hip (femur neck) were measured by dual-energy X-ray absorptiometry (DEXA). The VDR gene ApaI, BsmI and TaqI genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and association analysis was carried out at genotype and haplotype level. Our study suggests that TaqI polymorphism CC genotype frequency is lower in controls and further analysis of genotypes and BMD revealed a significant effect of TaqI polymorphism on Lumbar spine BMD. Two haplotypes (GCC and AAT) were associated with increased osteoporosis risk. In conclusion, VDR gene TaqI polymorphism in recessive mode had a significant effect on lumbar spine BMD within our study. Haplotypes GCC and AAT increase the risk of osteoporosis among White British males