Impact of CCL2 and Its Receptor CCR2 Gene Polymorphism in North Indian Population: A Comparative Study in Different Ethnic Groups Worldwide

Chemokine are small, inducible pro-inflammatory cytokines involved in many biological processes, such as migration of leukocytes, atherosclerosis, angiogenesis, tumor growth, and metastasis. Chemokine are also known to influence tumor cell’s activity. Specifically, tumor cells express chemokine receptors in a non random manner suggesting a role of chemokine in metastatic destination of tumor cells. The present study was conducted to determine distribution of (Chemokine receptor 2) CCR2 V64I, Chemokine ligand 2 CCL2 I/D, and CCL2 2518 A>G gene polymorphisms in North Indian population and compare with different populations globally. Polymerase chain reaction (PCR)-based analysis was conducted in 200 normal healthy individuals of similar ethnicity. Allelic frequencies in wild type (GG) of CCR2 V64I G>A were 63 % G; CCL2 I/D 42 % II; CCL2 2518 A>G 40.5 % A. The minor variant allele frequency in our population was as follows: 19.5 % for CCR2 V64I, 35.5 % for CCL2 I/D, 35.3 % for CCL2 2518 A>G. We further compared frequency distribution for these genes with various published studies in different ethnicity. Our results suggested that frequency in chemokine genes exhibit distinctive pattern in India that could be attributed to ethnicity variation. This could assist in high-risk screening of human exposed to environmental carcinogens and cancer predisposition in different ethnic groups. Thus, they signify an impact of ethnicity and provide a basis for future epidemiological and clinical studies.     

Lipoprotein (a): a Unique Independent Risk Factor for Coronary Artery Disease

The current epidemic affecting Indians is coronary artery disease (CAD), and is currently one of the most common causes of mortality and morbidity in developed and developing countries. The higher rate of CAD in Indians, as compared to people of other ethnic origin, may indicate a possible genetic susceptibility. Hence, Lp(a), an independent genetic risk marker for atherosclerosis and cardiovascular disease assumes great importance. Lp(a), an atherogenic lipoprotein, contains a cholesterol rich LDL particle, one molecule of apolipoprotein B-100 and a unique protein, apolipoprotein (a) which distinguishes it from LDL. Apo(a) is highly polymorphic and an inverse relationship between Lp(a) concentration and apo(a) isoform size has been observed. This is genetically controlled suggesting a functional diversity among the apo(a) isoforms. The LPA gene codes for apo(a) whose genetic heterogeneity is due to variations in its number of kringles. The exact pathogenic mechanism of Lp(a) is still not completely elucidated, but the structural homology of Lp(a) with LDL and plasmin is possibly responsible for its acting as a link between atherosclerosis and thrombosis. Upper limits of normal Lp(a) levels have not been defined for the Indian population. A cut off limit of 20 mg/dL has been suggested while for the Caucasian population it is 30 mg/dL. Though a variety of assays are available for its measurement, standardization of the analytical method is highly complicated as a majority of the methods are affected by the heterogeneity in apo(a) size. No therapeutic drug selectively targets Lp(a) but recently, new modifiers of apo(a) synthesis are being considered.     

Prevalence of insulin resistance in first degree relatives of type-2 diabetes mellitus patients: A prospective study in north Indian population

A total of 172 first degree relatives (FDRs) and 178 controls were included in this study. All the cases and controls were subjected to various anthropometric measurements, fasting and postprandial glucose estimation, fasting insulin measurement and fasting lipid profile. Results revealed the prevalence of Impaired Fasting Glucose (IFG) (cases 37% Vs controls 11.6%), Impaired Glucose Tolerance (IGT) (cases 34.3% Vs controls 11.2%) and diabetes (cases 11.05% controls 3.37%) was significantly higher in first degree relatives. Insulin resistance was measured using various methods, which included fasting plasma insulin (FPI), Homeostasis Model Assessment for Insulin Resistance (HOMA_IR), insulin sensitivity index (ISI) (Mffm/l). Prevalence of insulin resistance (Insulin Resistance) as observed comparing FPI and HOMA_IR in cases and controls was 43.6% and 11.24% (P=0.005) and 37.8% and 12.47% (P=0.000) respectively. Prevalence of IR (Insulin Resistance) observed in cases having Normal Glucose Tolerance (NGT), Impaired Fasting Glucose (IFG), Impaired Glucose Tolerance (IGT) and diabetes mellitus measuring FPI Vs HOMA_IR was 37.5% vs 30.2%, 45% vs 40%, 38.98% vs 37.28% and 36.84% vs 31.57% as accordingly. However, ISI (Mffm/l) was not found to be a promising index for IR due to its poor specificity. Though HOMA is taken as gold standard for measurement of IR globally, our study observed fasting plasma insulin representing high sensitivity (89.7%) and specificity (93.3%) as compared to HOMA. Thus FPI had emerged in this work as a simple and reliable test for diagnosing insulin resistance across the population susceptible to develop diabetes including FDRs.     

Evaluation of hypoglycemic and antioxidant effect of<Emphasis Type="Italic">Ocimum sanctum</Emphasis>

Ocimum sanctum leaves have been traditionally used in treatment of diabetes mellitus. Dietary supplementation of fresh tulsi leaves in a dose of 2 gm/kg BW for 30 days led to significant lowering of blood glucose levels in test group. Intake ofOcimum sanctum also led to significant increase in levels of superoxide dismutase, reduced glutathione and total thiols, but marked reduction in peroxiodised lipid levels as compared to untreated control group. The leaves were found to possess both superoxide and hydroxyl free radical scavenging action. The present observations establish the efficacy ofOcimum sanctum leaves in lowering blood glucose levels and antioxidant property appears to be predominantly responsible for hypoglycemic effect.     

Serum Malondialdehyde (MDA) in relation to lipidemic status and atherogenic index

Lipid peroxidation (MDA) was studied spectrophotometrically in relation to lipidemic status and atherogenic index in IHD and IHD risk subjects. It was found to be significantly elevated compared to control subjects (P<0.005) in both the groups, showing a linear correlation with cholesterolemic status. The values were found to run parallel to atherogenic index. In 10% cases with borderline atherogenic index the lipid peroxidation was found to be highly elevated. It is speculated that it may have a future role as a marker for IHD risk specially in premature group.     

Oxygen derived free radicals in clinical context

Oxygen derived free radicals have been implicated in a number of clinical disorders including atherosclerosis (1), ischemic heart disease (IHD) (2), post ischemic reperfusion injury (3) and respiratory distress syndrome (4). These radical are generated by sequential reduction of molecular oxygen; the primary product being superoxide anion (O₂ ^.−) which is subsequently reduced to hydrogen peroxide (H₂O₂), hydroxy1 radical (OH^.) and singlet oxygen (¹O₂). However the evidence for ODFR induced cell damage in various clinical disorders is still debated and rests largely on free radical scavenging studies, through electron paramagnetic resonance spectroscopic (EPRS) studies have provided direct evidence for ODFR generation following coronary artery ligation (5). By definition, a free radical is an atom, ion or molecule with one or more unpaired electrons (the presence of unpaired electron in a free radical being represented by a superscribed bold dot-R^.) and may be formed as a result of homolytic fission of a covalent bond or by electron transfer reactions, and may have cationic (NH₃ ⁺), anionic (O₂ ^.−) or neutral (NO) characteristics. The most important in vivo source for these radical species have been found to be univalent biochemical redox reactions involving oxygen. (a) A:B→A^.+B^. (b) A:+B→A^.+B^.     

Binding and degradation of native and acetylated low density lipoproteins by monocyte derived macrophages of normal and hypercholesterolemic rabbits

Low density lipoprotein (LDL) was isolated from normal rabbits and was modified with acetic anhydride. Blood monocyte derived macrophages from normal and hypercholesterolemic (HC) rabbits were cultured, and on the 8th day the cells were incubated with native and modified LDL to study their binding and degradation. Macrophages from both normal and hypercholesterolemic rabbits express a limited number of receptors for normal plasma LDL whereas they exhibit a large number of receptors for acetyl LDL. There was no significant difference between binding and degradation of acetyl LDL by normal or hypercholesterolemic cells. However, binding and degradation of native LDL by monocytes of hypercholesterolemic cells were significantly less (p<0.0001) in comparison to binding and degradation of native LDL by normal cells indicating that there is a feedback inhibitory pathway in the cell that inhibits the synthesis of LDL receptors in the presence of excess LDL.     

Polymorphism (C677T) in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene: A preliminary study on north Indian men

An elevated level of plasma homocysteine, sulfur containing amino acid generated through demethylation of methionine has been widely accepted as a risk factor for cardiovascular disease (CVD). The increase can result from genetic and/or nutrient related disturbances in the remethylation or transsulfuration pathways for homocysteine metabolism. A common mutation (C677T) in the gene encoding for the enzyme 5, 10-methylenetetrahydrofolate reductase (MTHFR) or deficiency of the B vitamins namely folic acid, B₁₂, B₆ can lead to hyperhomocysteinemia. In the present study, we have investigated the incidence of the (C677T) MTHFR polymorphism in the North Indian males. 141 angiographically proven coronary artery disease (CAD) patients and 55 age and sex matched healthy volunteers were examined for the association between MTHFR gene polymorphism and CAD. The MTHFR genotyping was performed using polymerase chain reaction (PCR) followed by restriction-isotyping with Hinf 1 endonuclease. A trend for higher ‘T’ allele frequency (0.19) was observed in patients than in controls (0.16). However no significant association was found between C677T mutation and CAD severity. The lack of statistical significance could be due to the small sample size studied. Hence a larger study including various ethnic groups is warranted.