South Indian Tamil Population Research Articles

Altered Placental Insulin Signaling in the Absence of Systemic Insulin Resistance in Hypertensive Disorders of Pregnancy among South Indian Tamil Population

A cross sectional study was conducted to explore the possible derangements in placental insulin signaling and also to investigate the presence or absence of maternal systemic insulin resistance in different types of hypertensive disorders of pregnancy (HDP). Study Design: Healthy pregnant women (n=32) and pregnant women with gestational hypertension (GH) (n=18), late onset Pre-eclampsia (LP) (n=18) and early onset Pre-eclampsia (EP) (n=19) were recruited for the study. Maternal venous blood and placental samples were collected from the study subjects at 35±7 weeks of gestation. Insulin resistance parameters such as fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, beta cell function and insulin sensitivity and glycated hemoglobin were estimated in the maternal venous blood samples. Placental protein expressions of insulin signaling molecules were analyzed by western blotting method. Results: Maternal venous blood insulin resistance parameters were not significantly different between the study groups. However, placental content of phospho insulin receptor beta was significantly decreased in GH, LP and EP groups in comparison to controls. We also found a significant decrease in placental protein expression of phosphatidyl inositol 3-kinase p85 alpha in LP group when compared to other groups.

Lack of Association between a Functional Polymorphism in Dopamine and Opioid Receptor Genes with Alcoholism in South Indian Tamilian Population.

Background: Single nucleotide polymorphism (SNP) of dopamine receptor (DRD2) and μ opioid receptor (OPRM1) genes are associated with susceptibility towards alcoholism. Hence, our study aimed to investigate the association of rs1799732 (DRD2) and rs1799971(OPRM1) with the risk of alcohol dependence in the south Indian Tamilian population and to compare the frequencies of these SNPs with major global populations. Methods: A total of 150 alcohol-dependent cases aged between 18 and 65 years who satisfied DSM-V were recruited from a de-addiction center (TTK hospital, Chennai). For the control group, 150 unrelated male blood donors with an AUDIT score of less than 8 were included. Genomic DNA was extracted and the alleles were genotyped using Taqman SNP genotyping assays by quantitative PCR. Results: Minor allele frequency (MAF) of rs1799732 and rs1799971 among controls were 16.7% and 50.3% respectively. Fisher’s exact test showed a highly significant difference in MAF of DRD2 and OPRM1 between south Indian controls and European as well as African populations. All the five genetic models of SNPs were evaluated using the Chi-square test revealed no statistically significant association between the SNPs and alcohol dependence. Conclusions: The present study did not find any association between DRD2 −141C Ins/Del and A118G OPRM1 polymorphism with alcoholism in the Tamilian population of south India.

Association of ADH1C and ALDH2 genes with alcohol dependence in south Indian Tamilian population

Objectives: Alcohol dependence (AD) poses a serious medical problem and significant public health issue contributing to morbidity and mortality throughout the world. The aim of the study was to establish the allele and genotype frequencies and to test the association of rs698 (ADH1C) and rs671(ALDH2) with the risk of alcohol dependence in south Indian Tamilian population. Methodology: A total of 150 alcohol dependent cases aged between 18- and 65-years fulfilling DSM-V criteria were recruited from the de-addiction centre. Blood donors (n=150) who had a history of alcohol intake with AUDIT score of less than eight were selected for the control group. The alleles were genotyped using TaqMan SNP genotyping assays by quantitative PCR. Association with alcohol dependence was evaluated with various genetic models using the Chi-square test. Multiple logistic regression analysis was performed to explore the effect of covariates. Results: The observed genotype frequency distributions of rs698 and rs671 were in agreement with Hardy Weinberg equilibrium (p>0.05).The dominant and allelic genetic model of ALDH2, rs671 between cases and controls showed a statistically significant association of the genetic variant with AD.

LDLR gene polymorphisms in CAD patients among South-Indian Tamil population

Introduction and aim: Coronary artery disease (CAD) is a multifactorial condition caused by the interplay of hereditary and environmental factors. The major objective of this research is to evaluate the Low-density of lipoprotein receptor (LDLR) single nucleotide polymorphisms (SNPs) rs688 and rs5925 and the lipid profile in coronary artery disease (CAD) and their connection with CAD. Materials and methods: The research included 50 patients with coronary artery disease and 30 healthy controls. To examine the lipid profile parameters, fasting venous blood was taken. Genomic DNA was isolated, amplified, and identified using an allele-specific polymerized chain reaction for the genetic study of LDLR SNPs. Results: Lipid profile parameters were shown to be substantially (p0.000) linked with coronary artery disease. There was, however, no significant change in the allele and genotype frequencies of the LDLR SNPs rs688 and rs5925 between the case and control groups investigated. Conclusion: The current investigation was unable to detect a significant connection between the LDLR gene SNPs rs688 and rs5925 with CAD.

Association of HLA-B*51:01, HLA-B*55:01, CYP2C9*3, and Phenytoin-Induced Cutaneous Adverse Drug Reactions in the South Indian Tamil Population.

Phenytoin (PHT) is one of the most commonly reported aromatic anti-epileptic drugs (AEDs) to cause cutaneous adverse reactions (CADRs), particularly severe cutaneous adverse reactions (SCARs). Although human leukocyte antigen (HLA)-B*15:02 is associated with PHT-induced Steven Johnson syndrome/toxic epidermal necrosis (SJS/TEN) in East Asians, the association is much weaker than it is reported for carbamazepine (CBZ). In this study, we investigated the association of pharmacogenetic variants of the HLA B gene and CYP2C9*3 with PHT-CADRs in South Indian epileptic patients. This prospective case-controlled study included 25 PHT-induced CADRs, 30 phenytoin-tolerant patients, and 463 (HLA-B) and 82 (CYP2C9*3) normal-controls from previous studies included for the case and normal-control comparison. Six SCARs cases and 19 mild-moderate reactions were observed among the 25 cases. Pooled data analysis was performed for the HLA B*51:01 and PHT-CADRs associations. The Fisher exact test and multivariate binary logistic regression analysis were used to identify the susceptible alleles associated with PHT-CADRs. Multivariate analysis showed that CYP2C9*3 was significantly associated with overall PHT-CADRs (OR = 12.00, 95% CI 2.759–84.87, p = 003). In subgroup analysis, CYP2C9*3 and HLA B*55:01 were found to be associated with PHT-SCARs (OR = 12.45, 95% CI 1.138–136.2, p = 0.003) and PHT-maculopapular exanthema (MPE) (OR = 4.041, 95% CI 1.125–15.67, p = 0.035), respectively. Pooled data analysis has confirmed the association between HLA B*51:01/PHT-SCARs (OR = 6.273, 95% CI 2.24–16.69, p = <0.001) and HLA B*51:01/PHT-overall CADRs (OR = 2.323, 95% CI 1.22–5.899, p = 0.037). In this study, neither the case nor the control groups had any patients with HLA B*15:02. The risk variables for PHT-SCARs, PHT-overall CADRs, and PHT-MPE were found to be HLA B*51:01, CYP2C9*3, and HLA B*55:01, respectively. These alleles were identified as the risk factors for the first time in the South Indian Tamil population for PHT-CADRs. Further investigation is warranted to establish the clinical relevance of these alleles in this population with larger sample size.

Prothrombotic Factors Have Significant Association with Arterial and Venous Strokes in Indian Tamilians.

Prothrombotic factors have been correlated with vascular events in young patients, with recurrent strokes, and with venous thromboembolisms. However, their prevalence in adult strokes, in healthy populations, and in specific ethnic groups is not well defined. We investigated the association of prothrombotic factors with strokes in a South Indian Tamil population. In this hospital-based cross-sectional study, plasma homocysteine (Hcys), protein C and protein S activity levels, activated protein C resistance (APCR) as a surrogate for factor V Leiden (FVL), fibrinogen, and antithrombin III (ATIII) were determined from 75 consecutive patients with ischemic stroke (IS), 25 with cortical venous thrombosis (CVT), and 75 healthy control participants. The Student t test or Mann-Whitney U test was used for comparing prothrombotic factor levels between the stroke and control groups. The χ2 or Fisher exact test was used for comparisons of proportions of thrombophilia and estimation of odds ratios. Mid-P correction was done for multiple estimations. Hcys levels in patients with IS were significantly higher compared with those in healthy control participants (P = 0.02). Proportions of ATIII deficiency and hyperfibrinogenemia were significantly higher in the IS group, and no healthy control participants had hyperfibrinogenemia. Protein C deficiency was more frequent in those with IS (17%; P < 8 × 10-5) and CVT (P < 10-7) compared with healthy control participants, and protein C activity levels (P = 0.016) were also significantly lower in patients with CVT. Other parameters had no significant associations with IS and CVT. The frequency of protein S deficiency was high in healthy control participants (60%) and in both patients with IS (45%; P = 0.1) and patients with CVT (48%; P = 0.4). No patients or control participants had abnormal APCR. In Tamilian participants, several prothrombotic factors were associated with IS. Protein C deficiency alone was associated with CVT. Replication of the pattern in genetically linked populations around the world may affect management of stroke in those populations.

Increased hepcidin levels in preeclampsia: a protective mechanism against iron overload mediated oxidative stress?

Background Pregnancy is a metabolic state which demands increased iron bioavailability. While in preeclampsia, due to the placental vascular events there is an iron surplus environment along with inflammation and placental hypoxia. Routinely in India iron is supplemented to all pregnant women irrespective of their general physical condition. Hepcidin a regulator of iron metabolism protects the cells from iron mediated cytotoxicity. Objective To find out whether hepcidin gets induced as a protective mechanism in preeclampsia patients in order to combat the environment of iron overload, oxidative stress, and endothelial dysfunction. Methods A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients in the gestational age 32 ± 4 weeks were recruited (n = 80). Biochemical analysis to assess the serum levels of the following were carried out (1) indices of iron homeostasis – serum iron, ferritin, transferrin, hepcidin, (2) endothelial dysfunction –serum assymetric dimethyl arginine (ADMA) (3) oxidative stress – Malon di aldehyde (MDA) and ferric reducing ability of plasma (FRAP). Kolmogorov-Smirnov test, Mann-Whitney U test, Spearman’s correlation, linear regression and ROCAUC analysis were performed to understand their relationship with each other. Results Levels of serum iron, ferritin, transferrin saturation, hepcidin, and MDA/FRAP ratio were elevated significantly in preeclampsia patients compared to controls, while serum transferrin levels were significantly decreased in them. Hepcidin levels showed a significant positive correlation with serum ADMA, and MDA/FRAP. Serum hepcidin, transferrin saturationand MDA/FRAP ratio is useful in differentiating pre-eclampsia patients from healthy pregnant women. Conclusion Iron supplementation in preeclampsia patients might have led to a state of iron overload, which might have caused oxidative stress and endothelial dysfunction in preeclampsia patients. The rise in hepcidin levels in this scenario may be viewed as a protective mechanism to combat the iron overload mediated cytotoxicity.

Diagnostic ability of hepcidin in predicting fetal outcome in preeclampsia

Background Low birth weight and prematurity are the major contributors to neonatal mortality and morbidity. Preeclampsia which is associated with both maternal and fetal mortality and morbidity is a major contributor to such poor fetal outcomes. Hepcidin an acute phase peptide hormone gets elevated in conditions of iron overload, inflammation, infections, and cytotoxicity. Hepcidin levels can get elevated in pregnancies with such pathologies which invariably will be having a poor fetal outcome. Objective To study the role of hepcidin as a diagnostic marker in predicting a poor fetal outcome. Materials and methods A cross-sectional study with follow up was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty preeclampsia patients were recruited between the gestational age of 34 ± 4 weeks and followed up till delivery. Serum levels of hepcidin were analyzed for all the participants and comparisons were done between preeclampsia and healthy pregnancies as well as between pregnancies with good and poor fetal outcomes. Fetal outcome variables such as birth weight, gestational age at the time of delivery and NICU admission status of the newborn were collected during the follow-up period. ROC curves were constructed to determine the ability of maternal serum hepcidin levels in predicting poor fetal outcomes with good sensitivity, specificity and likelihood ratios. Results Maternal hepcidin levels were found to be significantly elevated in preeclampsia patients (p < .001) as well as in mothers with the poor fetal outcome (p < .001). On ROC curve analysis, AUC were 0.686, 0.788, 0.749 and LR + were 2.18, 2.44, 2.14, respectively for predicting low birth weight, preterm delivery and NICU admission status of the newborn. Hepcidin was able to predict the overall poor fetal outcome in our preeclampsia patients above a cut off level of 615 pg/ml Conclusion Above a cut off level of 615 pg/ml and at the gestational age of 34 ± 4 weeks, maternal hepcidin levels were able to predict poor fetal outcomes such as low birth weight, preterm delivery, and NICU admission.

Increased placental expressions of nuclear factor erythroid 2–related factor 2 and antioxidant enzymes in gestational diabetes: Protective mechanisms against the placental oxidative stress?

Objective: Gestational diabetes mellitus is associated with increased oxidative stress. Oxidative stress may contribute to the risk for pregnancy pathologies associated with gestational diabetes mellitus. In this study we investigated the expression of placental nuclear factor erythroid 2–related factor 2 (Nrf2) and antioxidant enzymes of gestational diabetes mellitus and healthy pregnant women and correlated them with the maternal and cord plasma as well as placental tissue oxidative stress parameters.Study design: A cross sectional study was carried out in a South Indian Tamil population. Forty healthy pregnant women and forty gestational diabetes mellitus patients in the gestational age of 32 ± 4weeks were recruited. Maternal plasma, cord plasma and placental oxidative stress parameters were measured. Placental expression of Nrf2, phospho Nrf2, catalase and superoxide dismutase 1(SOD1) were analyzed by western blotting and immunohistochemistry.Results: Placental expression of Nrf2, catalase and SOD1 were found to be significantly higher in gestational diabetes mellitus. The maternal plasma, cord plasma and placental tissue oxidative stress parameters, total antioxidant status (TAS) levels were significantly lower; whereas MDA (malondialdehyde) and MDA/TAS levels were significantly higher in gestational diabetes mellitus. Placental Nrf2 expression correlated positively with the placental catalase expression and negatively with placental TAS levels in both groups.Conclusion: Maternal, fetal and placental oxidative stress was observed in gestational diabetes mellitus. The gestational diabetic placenta had an increased Nrf2 protein expression. The activated placental Nrf2/ antioxidant response element (ARE) pathway might have led to an increased expression of antioxidant enzymes SOD1 and catalase. This may be viewed as a protective mechanism in placenta from the further onslaught of oxidative stress.

Association of PTPN22 gene polymorphism with non-segmental vitiligo in South Indian Tamils.

IntroductionNon-segmental vitiligo (NSV) is a depigmentation skin disease with loss of melanocytes in the skin.AimTo evaluate whether the protein tyrosine phosphatase non-receptor type (PTPN22) single nucleotide polymorphism at +1858C/T had any association with non-segmental vitiligo in South Indian Tamils.Material and methodsGenomic DNA was extracted using the phenol-chloroform method, and PTPN22 +1858C/T polymorphism was assayed by Taqman 5’allele discrimination assay. Protein levels were quantified by ELISA.ResultsWe found that the allelic frequency of variants of PTPN22 (rs2476601) were significantly different between controls and cases showing a vitiligo risk in the South Indian Tamil population. PTPN22 levels were higher in the heterozygous CT genotype in NSV, when compared with that of the major variant CC genotype of rs2476601.ConclusionsThis study suggests that the heterozygous CT genotype, of the PTPN22 SNP rs2476601, has a strong risk association with non-segmental vitiligo in South Indian Tamils.

Genetic spectrum of low density lipoprotein receptor gene variations in South Indian population

BackgroundLow density lipoprotein receptor (LDLR) is a membrane bound receptor maintaining cholesterol homeostasis along with Apolipoprotein B (APOB), Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) and other genes of lipid metabolism. Any pathogenic variation in these genes alters the function of the receptor and leads to Familial Hypercholesterolemia (FH) and other cardiovascular diseases. ObjectiveThis study was aimed at screening the LDLR, APOB and PCSK9 genes in Hypercholesterolemic patients to define the genetic spectrum of FH in Indian population. MethodsFamilial Hypercholesterolemia patients (n=78) of South Indian Tamil population with LDL cholesterol and Total cholesterol levels above 4.9mmol/l and 7.5mmol/l with family history of Myocardial infarction were involved. DNA was isolated by organic extraction method from blood samples and LDLR, APOB and PCSK9 gene exons were amplified using primers that cover exon-intron boundaries. The amplicons were screened using High Resolution Melt (HRM) Analysis and the screened samples were sequenced after purification. ResultsThis study reports 20 variations in South Indian population for the first time. In this set of variations 9 are novel variations which are reported for the first time, 11 were reported in other studies also. The in silico analysis for all the variations detected in this study were done to predict the probabilistic effect in pathogenicity of FH. ConclusionThis study adds 9 novel variations and 11 recurrent variations to the spectrum of LDLR gene mutations in Indian population. All these variations are reported for the first time in Indian population. This spectrum of variations was different from the variations of previous Indian reports.

L55M and Q192R polymorphism of Paraoxonase gene and the risk of myocardial infarction in South Indian Tamil population

Paraoxonase, also known as aromatic esterase 1 encoded by PON1 gene is a high density lipoprotein linked enzyme that possess antiatherogenic activity. It protects low density lipoprotein (LDL) from oxidation and destroys biologically active oxidized lipids on lipoproteins and in arterial cells. Polymorphisms in PON1 gene, L55M and Q192R on exon 3 and 6 respectively are known to be risk in causing cardiovascular diseases. The study was aimed to determine the association of L55M and Q192R in pathogenicity of myocardial infarction in South Indian Tamil population. Tetra primer Amplification Refractory Mutation System–PCR method uses allele specific primer to discriminate the L55M and Q192R alleles. Total of 350 individuals enrolled at SRM Medical college hospital were considered for the study (200 MI patients and 150 age, sex matched controls). The genotype frequency in the population for L55M is LL=0.49, LM=0.40, MM=0.10, for Q192R is QQ=0.38, QR=0.46, RR=0.15 and it is consistent with Hardy-Weinberg equilibrium. The Logistic regression analysis showed MM vs LL having OR=1.44, M vs L OR=1.56 stating M allele is associated with developing risks of MI. In Q192R, RR vs QQ OR=3.25, R vs Q, OR=1.88 showing R allele having 3 times higher risk in developing MI.

Vascular endothelial growth factor (VEGF) gene polymorphisms (rs699947, rs833061, and rs2010963) and psoriatic risk in South Indian Tamils

BackgroundPsoriasis is a chronic inflammatory disease of the skin. Vascular endothelial growth factor (VEGF), a pro-angiogenic factor, is involved in the pathogenesis of psoriasis. Being highly polymorphic, several SNPs of VEGF have been reported to be associated with increased risk of psoriasis. ObjectivesWe determined the association of VEGF gene polymorphisms with risk of psoriasis in South Indian Tamils. Methods300 cases of psoriasis and 300 controls were recruited in this case-control study. Genotyping of SNPs of VEGF gene was done using Taqman 5′ allele discrimination assay. Estimation of VEGF levels in plasma was done by ELISA. ResultsVEGF (rs2010963) polymorphism and the CTC haplotype were found to confer an increased risk of psoriasis. However, two other VEGF SNPs, rs833061, and rs699947, showed no association with psoriasis susceptibility. VEGF levels were higher in patients with psoriasis, as compared with controls and significantly correlated with disease severity. ConclusionsOur results indicate that VEGF (rs2010963) polymorphism and CTC haplotype of the VEGF SNPs (rs699947, rs833061, and rs2010963) confer an increased risk of psoriasis in the South Indian Tamil population. Plasma VEGF levels are higher in patients with psoriasis, as compared with controls and are significantly correlated with disease severity.

Association of MICA-129 polymorphism and circulating soluble MICA level with rheumatoid arthritis in a south Indian Tamil population.

Rheumatoid arthritis (RA) is a clinically heterogeneous chronic inflammatory disorder characterized by synovitis leading to joint destruction. Both genetic and environmental factors are involved in the pathogenesis of RA. Significant dysregulation of NKG2D, an activating receptor of natural killer and certain autoreactive T cells as well as its ligand major histocompatibility complex class I chain-related gene A (MICA) has been implicated in perpetuating the pathology of RA. Since the genetic polymorphism in MICA gene (MICA-129 met/val polymorphism at codon 129) is known to affect its binding affinity to NKG2D, we explored its influence on RA susceptibility and disease severity. The MICA-129 met/val polymorphism was examined in 270 patients with RA and 232 healthy controls by TaqMan 5'-nuclease assay. Serum soluble MICA (sMICA) was measured in a subset of 89 patients and 80 controls by enzyme-linked immunosorbent assay. We observed that the frequency of MICA-129 val allele (73% vs. 65%, Pc = 0.006, odds ratio = 1.48, 95% CI = 1.12-1.95) was higher in patients than in controls. sMICA levels were significantly higher in patients with RA than in controls (P < 0.0001). sMICA levels were higher in patients with val/val genotype than in those with met/val or met/met genotype (P = 0.03). The MICA-129 val/val genotype was associated with high titers of sMICA in patients with deforming RA phenotype (P = 0.02), suggesting a role in determination of severity of RA. MICA-129 val/val genotype, associated with higher levels of circulating sMICA, may influence disease susceptibility and associate with increased severity of RA in south Indian Tamils.

Frequencies of Genetic Polymorphisms of the Cholesterol and Statin Metabolic Pathway Genes among Healthy South Indian Tamil Population

: Background: Indians are genetically predisposed to Coronary Artery Disease (CAD), hence it is worth studying the effect of genetic polymorphisms which affect CAD development including Low- Density Lipoprotein Cholesterol (LDL-C) in our population. Studies have found that there is a considerable variation in the genetic makeup of Indians with distinct genetic groups having been identified-one such being Dravidian Tamil population. Aim:We aimed to determine the distribution of allele and genotype frequencies of genes associated with LDL-C lipid levels as well as those associated with statin metabolic pathway in 100 healthy South Indian Tamil volunteers. Results:The minor allele frequencies (MAFs) of the genetic polymorphisms of HMGCR rs5908, rs17238540 and rs12916 were 0.5, 3.5 and 41% respectively. The MAF of LDLR rs688, CYP7A1 rs3808607, ABCB1 rs1128503, SLCO1B1 rs4149056 were 26, 42, 41.5 and 7% respectively. The frequencies of the genetic polymorphisms studied show considerable variation from other Indian ethnic groups in 5 out of the 7 genetic polymorphisms studied. Conclusion: Considerable variations in frequencies of genetic polymorphisms were found between Tamil population and other major ethnic populations worldwide with respect to HMGCR rs17238540 and LDLR rs688.Key words: Genetic polymorphisms, Genotype frequency, Tamilians, Healthy volunteers, LDL-C, Statin pathway.

The protein tyrosine phosphatase, nonreceptor type 22-1858C-&gt;T (rs2476601) polymorphism is not a genetic risk factor for systemic lupus erythematosus in Indian Tamils

Background: Systemic lupus erythematosus (SLE), a systemic autoimmune disease, occurs due to disruption of immune homeostasis against self-antigens. The etiology of SLE is complex and multiple genetic factors contribute to disease susceptibility and clinical phenotypes. Protein tyrosine phosphatase, nonreceptor type 22 (PTPN22) is a lymphoid-specific phosphatase that negatively regulates T-cell receptor signaling and is responsible for the maintenance of T-cell homeostasis. Genetic aberrations affecting the function of PTPN22 result in the proliferation of autoreactive T-cells and development of autoimmune diseases. Methods: We carried out a case–control genetic study to analyze the association of PTPN22 R620W polymorphism (rs2476601) with disease susceptibility and clinical and autoantibody profile in Indian Tamils with SLE. Three hundred SLE patients satisfying the 1997 revised American College of Rheumatology classification criteria for SLE were enrolled in the study. Disease activity was measured using the SLE Disease Activity Index. We recruited 460 age-, sex-, and ethnicity-matched individuals without a family history of autoimmune diseases as control population. Genomic DNA was extracted from the blood sample by salting-out method. The PTPN22-1858C->T (rs2476601) polymorphism was screened by polymerase chain reaction-restriction fragment length polymorphism. Results: The frequency of the ancestral allele “C” was similar in both cases and controls (99.3% and 99.8%, respectively) and the mutant allele “T” was less frequent in South Indian Tamil population; it did not influence clinical or serological phenotypes. Conclusion: Our findings suggest that the PTPN22 (rs2476601) polymorphism is less frequent and did not confer a risk for lupus or its associated clinical or serological phenotypes in South Indian Tamils.

Effect of antituberculosis treatment on CYP2C19 enzyme activity in genetically polymorphic South Indian Tamilian population.

Patients on antituberculosis therapy (ATT) are more prone to drug interactions in the presence of coexisting illnesses which require drug therapy. Rifampicin is a pleiotropic inducer of CYP enzymes, and isoniazid is an enzyme inhibitor. Genetic variations are common in the gene coding for CYP2C19 enzyme. These variations would be important in predicting the individual variations in CYP2C19 activity. The objectives of the study were to find the net effect of 1-month ATT on CYP2C19 enzyme activity and its association with CYP2C19 genetic polymorphisms. Newly diagnosed tuberculosis patients (n = 125) were included in the study. Before commencing ATT, they were given a single dose of omeprazole 20 mg as a probe drug for CYP2C19. Blood sample was collected after 3 h to carry out phenotyping for CYP2C19 enzyme by measuring omeprazole hydroxylation index (OHI) using LC-MS/MS. The phenotyping procedure was repeated after 1 month of ATT. CYP2C19 genotyping was carried out by PCR-RFLP method. Significant reduction in OHI was observed after 1 month of ATT in all the metabolizer groups. The percentage reduction in OHI was maximum with poor metabolizers, 84.1 (IQR - 74.6, 86.6), and minimum with ultra-rapid metabolizers, 39.6 (IQR - 12.7, 54.7). CYP2C19 enzyme induction is predominant in patients after 1 month of antituberculosis treatment (ATT). Genetic variations in the enzyme could not clearly explain the interindividual differences in induction. There is a potential risk of drug failure/adverse effect in poor metabolizers regardless of their genotype after ATT.

Association of C-Reactive Protein (rs1205) Gene Polymorphism with Susceptibility to Psoriasis in South Indian Tamils.

Psoriasis is a multi-factorial heritable T-helper Th-1/Th-17 mediated inflammatory disease, affecting the skin. It is associated with co-morbidities such as Cardiovascular Disease (CVD). C-Reactive Protein (CRP) is a good inflammatory marker. CRP rs1205 polymorphism is associated with circulating plasma CRP levels. Although there is association between the rs1205 Single Nucleotide Polymorphism (SNP) and CVD, there are no prior reports regarding the association of CRP rs1205 SNP with psoriasis susceptibility. To study the association of the genetic variant rs1205 in the CRP gene with susceptibility to the disease and protein levels in South Indian Tamils with psoriasis. In this case-control genetic study, 300 cases of psoriasis and 300 age and gender matched controls were genotyped for CRP SNP rs1205 using Taq Man 5'allele discrimination assay at Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India from February 2014 to January 2016. Plasma high sensitivity (hs)-CRP levels were estimated by ELISA. Disease severity was assessed by Psoriasis Area Severity Index (PASI). CRP genetic variation rs1205 was not associated with psoriasis risk in our South Indian Tamil population. However, the circulating levels of hs-CRP was significantly higher in patients with psoriasis, as compared with controls (p < 0.0001) and the protein levels were significantly associated with disease severity, as assessed by PASI scoring. No genotype was found significantly associated with PASI or CRP levels. Our results suggest that plasma CRP levels are higher in patients with psoriasis and correlate with disease severity, whilst CRP rs1205 is not associated with susceptibility to psoriasis in South Indian Tamils.

Investigation of association of the IL-12B and IL-23R genetic variations with psoriatic risk in a South Indian Tamil cohort

BackgroundPsoriasis is a T-cell mediated chronic systemic inflammatory skin disease. Emerging evidences suggest the interleukin (IL)-12B and IL-23R genes encoding the common p40 subunit of IL-12 and IL-23 are the key cytokines in T-helper (Th)1 and Th17 differentiation and function. Certain allelic variants of these genes significantly influence the risk of psoriasis. Hence we undertook to study the association of IL-12B and IL-23R gene polymorphisms with disease susceptibility in South Indian Tamil patients with psoriasis. Methods360 psoriatics and 360 healthy controls were included in this case control study. IL-12B gene (rs3212227) and IL-23R gene (rs2201841, rs10889677 and rs11805303) polymorphisms were typed by using TaqMan 5′allele discrimination assay and cytokine levels were assayed by ELISA. ResultsWe observed that the patients carrying the risk genotypes of IL-12B (rs3212227) and IL-23R (rs2201841) conferred an increased susceptibility to psoriasis. We did not find any significant association between IL-23R (rs10889677 and rs11805303) gene polymorphisms and psoriasis risk in South Indian Tamil population. We did not observe any significant difference in haplotypes between the psoriasis cases and controls. We observed a significant increase in the mean IL-23 levels in psoriatics and the higher levels of IL-23 were found in the minor variant genotype CC when compared with that of heterozygous CT and major variant TT genotypes of rs2201841. Individual genotypes of rs10889677 and rs11805303 and IL-12 (rs3212227) were not significantly associated with their plasma levels. ConclusionOur results suggest that IL-12B (rs3212227) and IL-23R (rs2201841) polymorphisms confer increased risk of psoriasis in our ethnic South Indian Tamils.

Plasma homocysteine levels in depression and schizophrenia in South Indian Tamilian population

Context:Hyperhomocysteinemia has been associated with psychiatric diseases in non-Indian populations.Objectives:We aimed to determine if total plasma Homocysteine (Hcys) is associated with schizophrenia or depression in South Indian Tamil patients and if so, to correlate their severity and phenomenology to Hcys levels.Settings and Design:40 patients each with schizophrenia and depression and 40 healthy controls were recruited from the psychiatry department of a quaternary referral centre. Association between Hcys and psychiatric disorders was determined using a Case- control design. Hcys levels were correlated with age, gender and severity and duration of the disease by appropriate statistical methods using SPSS17.Materials and Methods:Schizophrenia and depression were defined using ICD10 DCR version. Severity of depression was assessed by Hamilton Depression Rating Scale and that of schizophrenia using Positive and Negative Schizophrenia scales (PANSS). Hcys levels were determined using automated chemiluminiscence immunoassay (74-76).Statistical Analysis:Differences between the mean values of plasma homocysteine levels among schizophrenia, depression and control groups were compared using analysis of variants. The association between the severity and duration of schizophrenia and depression and the plasma homocysteine levels were determine using Pearson correlation.Conclusions:In Tamilian population, schizophrenia and depression are associated with total plasma Hcys levels which correlated with the duration and severity of psychosis.