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Background and aim Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Methods Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. Results The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. Conclusion PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. [ABSTRACT FROM AUTHOR]

Background Cytokines regulate the expression of inflammatory molecules which destabilize the atheromatic plaques. This study focuses on studying the association of inflammatory cytokine polymorphisms like TNF-α − 308 (G/A), TNF-β + 252 (A/G), IL-6 − 174 (G/C) and IL-6 − 597 (G/A), and IFN-ɣ + 874 (T/A) with coronary artery disease (CAD) among north Indian patients. Materials and methods 143 CAD and 137 normal healthy controls were recruited in this study. DNA extraction was carried out by high salting out method. TNF-α − 308 (G/A) (rs1800797), TNF-β + 252 (A/G) (rs909253), IL-6 − 174 (G/C) (rs1800795), IL6 − 597 (G/A) (rs1800797), and IFN-ɣ + 874 (T/A) (rs2430561) SNPs were genotyped by TaqMan®SNP genotyping assays. Different statistical analyses were performed using SPSS v 22.0 and SNPStats. p ≤ 0.05 was considered significant. Results Significant risk association with CAD was found for TNF-α − 308 (G/A) “A” allele (OR = 5.6, CI 1.8–17.4, p = 0.001) and TNF-β + 252 (A/G) “G” allele (OR = 3.4, CI = 1.9–6.0, p < 0.001). However, no statistical significance was found for IL-6 − 174 (G/C) or IL6 − 597 (G/A), with CAD. TNF-α − 308 (G/A), and TNF-β + 252 (A/G) haplotype “GG” “AG” increased CAD risk significantly (GG haplotype, adjusted OR = 2.6, CI 1.4–5.0, p = 0.003 and AG haplotype OR = 8.5, CI 2.2–33.35, p = 0.002) after adjustments for age, sex, TC, TG, HDL, APOB, smoking and diet. Discussion The present study found significant risk association for TNF-α − 308 (G/A), and TNF-β + 252 (A/G) genotypes, alleles and haplotypes, with CAD in a North Indian population. [ABSTRACT FROM AUTHOR]

Network analysis based on individuals under haplogroup H1. [Display omitted] • Chennai and neighboring populations from South and Central India exhibit unique linguistic constitution. • Network analyses of haplotypes indicate limited affinities between Indian populations. • AMOVAs indicate that language, social stratification and religion correlate with Y-STR differentiation. • AMOVAs indicate no statistically significant between Y-SNP partitioning and social rank and religion. • Rst distances based on Y-STR haplotypes suggest that India represents a mosaic of heterogeneous populations. Several migratory waves from various origins along with cultural practices restricting marriages between people of different castes and tribes as well as continued endogamy have led to a complex and diverse society in the Indian subcontinent. Despite being widely represented in genetic studies, several interrogatives remain with regards to India's current genetic constituents and distributions, source populations and population relationships. To identify the forces that may have shaped Indian population's genetic relationships, we undertook a comprehensive comparative study of the Y-chromosomes across India utilizing Y-STR and Y-SNP chromosomal markers using the general population of Chennai in the state of Tamil Nadu as a point of reference. Our analyses identify differences in source populations for different regions within India, unique linguistic characteristics as well as demographic and cultural forces that may have shaped population structure. [ABSTRACT FROM AUTHOR]

Methylenetetrahydrofolate reductase (MTHFR) reduces 5′,10′-methylenetetrahydrofolate to 5′-methyltetrahydrofolate, and is involved in remethylation of homocysteine to methionine, two important reactions involved in folate metabolism and methylation pathways. The common MTHFR C677T single nucleotide polymorphism (SNP) (rs1801133) has been associated with raised levels of homocysteine, a well known risk factor for coronary artery disease (CAD). CAD is a major cause of mortality worldwide. The age of onset of this chronic disorder is on the decline, particularly in the Indian population. Indians in South Africa (SA) have a higher prevalence of premature CAD compared to Black South Africans. The MTHFR C677T SNP has not been investigated in the SA Indian population. The present study therefore investigated the MTHFR C677T SNP in young SA Indian males with CAD compared to young Indian and Black male controls. A total of 290 subjects were recruited into this study which included 106 CAD patients (diagnosed on angiography, mean age 37.5, range 24–45 years), 100 Indian male controls (mean age 37.5, range 28–45 years), and 84 Black male controls (mean age 36.4, range 25–45). Polymerase chain reaction (PCR) followed by restriction fragment length polymorphism (RFLP) was used to genotype CAD patients and healthy controls. Data for clinical markers were obtained from pathology reports. There was a significant association between the 677 MTHFR variant (T) allele and CAD patients compared to the healthy Indian controls (p = 0.0353, OR = 2.105 95% CI 1.077–4.114). Indian controls presented with a higher frequency of the variant allele compared to Black controls (7% vs. 2% respectively, p = 0.0515 OR = 3.086 95% CI 0.9958–9.564). The MTHFR C677T SNP did not influence levels of total cholesterol, LDL, HDL, triglycerides, fasting glucose, fasting insulin, HbA1c or hsCRP. The higher frequency of the MTHFR 677 variant allele in South African Indians may be a contributing factor to the higher risk profile for the development of premature CAD in Indians. [ABSTRACT FROM AUTHOR]

Genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was undertaken to validate the association of SNPs with development of hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate genes was performed in 126 infants with hyperbilirubinemia and 181 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of the UGT1A1 promoter, specifically the -3279 T➔G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the coding region variants (rs2306283 and rs4149056) of the OATP2 gene were significantly higher among the cases than the controls. The presence of the mutant haplotypes either in homozygous, heterozygous or compound heterozygous state had a significant effect on neonatal hyperbilirubinemia as well as on the requirement of phototherapy than those with the wild haplotype. Further, a significantly higher number of hyperbilirubinemic cases had ≥3 variants than the controls (73.80% vs 40.36%, p<0.0001) and the mean total serum bilirubin levels and requirement of phototherapy also increased according to the number of variants co-expressed. This study demonstrates that UGT1A1 and OATP2 polymorphisms were associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

• An updated prehistoric AMH dispersal route in and out of NE India has been unveiled. • TrOC-linked autosomal loci & mtDNA-based marker predicted feasible migration route. • Prehistoric AMH dispersal probably linked with the high TrOC prevalence in NE India. • Back-migration from SE Asia (∼4kya) most likely introduced the TrOC-causing traits. • MtDNA-HG 'R' significantly associated with the risk of TrOC (OR > 9.5) in NE India. Northeast (NE) India is a subject of debate for predicting its involvement in prehistoric anatomically modern human (AMH) dispersal. The unique lifestyle and genetic characteristics of native ethnic groups in this region are believed to be responsible for their susceptibility to tobacco-related oral cancer (TrOC). The present study assessed mitochondrial macro-haplogroup (mHG) diversity and TrOC susceptibility autosomal loci to evaluate the impact of prehistoric AMH dispersal on the present day's high TrOC prevalence in major NE Indian ethnics. We considered 175 unrelated individuals from 35 ethnic groups and previously published 374 sequences for sequencing-based assessment of mtDNA-based marker by subsequent analyses like haplogroup diversity, phylogenetic, genetic structure by AMOVA, and MDS, descriptive statistics of demographic parameters, and migration analysis. Besides, we selected prolonged tobacco-chewing 124 case-control individuals from similar ethnic backgrounds for genotyping 115 autosomal loci in Sequenom iPLEX MassARRAY™ platform and mined 1000genome data (n = 398) for consequent global admixture and ancestry-specific allele frequencies-based analyses. Our mtDNA-based findings suggested that NE populations were distinct from other Indian populations, owing to the first wave of migration from ancient southern China (∼54kya) and two successive spatial expansion events at ∼45kya and ∼43kya. Consequently, it probably acted as another source for prehistoric AMH dispersal in N/NE Asia. Besides, the second wave of back-migration from SE Asia (∼40kya) probably replaced the mitochondrial footprints of survivors from the first migrants and introduced the TrOC susceptibility traits in this region. Afterward, the autosomal marker-based observations on the transition of the disease-associated admixture component 'K6' from SE Asia reconfirmed these results. Moreover, we also observed that the mitochondrial mHG 'R' is significantly associated with the risk of TrOC (OR > 9.5) in NE India. Furthermore, the possible onset of the phenotypic expression of those traits was predicted at ∼4kya, thus, contributing to present-day's TrOC prevalence. This study reflects its uniqueness by revealing an updated AMH dispersal route for the peopling in and out of NE India, which probably introduced the disease-causing traits in the ancestral NE Indian population. Those traits were then imprinted in their genome to get transferred through their respective generations, forming the present-day's TrOC-prevalent NE Indian population. [ABSTRACT FROM AUTHOR]

Abstract: Rett syndrome (RTT) is a severe neurodevelopmental disorder characterized by the progressive loss of intellectual functioning, fine and gross motor skills and communicative abilities, deceleration of head growth, and the development of stereotypic hand movements, occurring after a period of normal development. The classic form of RTT involves mutation in MECP2 while the involvement of CDKL5 and FOXG1 genes has been identified in atypical RTT phenotype. FOXG1 gene encodes for a fork-head box protein G1, a transcription factor acting primarily as transcriptional repressor through DNA binding in the embryonic telencephalon as well as a number of other neurodevelopmental processes. In this report we have described the molecular analysis of FOXG1 gene in Indian patients with Rett syndrome. FOXG1 gene mutation analysis was done in a cohort of 34 MECP2/CDKL5 mutation negative RTT patients. We have identified a novel mutation (p. D263VfsX190) in FOXG1 gene in a patient with congenital variant of Rett syndrome. This mutation resulted into a frameshift, thereby causing an alteration in the reading frames of the entire coding sequence downstream of the mutation. The start position of the frameshift (Asp263) and amino acid towards the carboxyl terminal end of the protein was found to be well conserved across species using multiple sequence alignment. Since the mutation is located at forkhead binding domain, the resultant mutation disrupts the secondary structure of the protein making it non-functional. This is the first report from India showing mutation in FOXG1 gene in Rett syndrome. [Copyright &y& Elsevier]

Abstract: Fanconi anemia (FA) is a genetic disorder characterized by progressive bone marrow failure and a predisposition to cancers. Mutations have been documented in 15 FA genes that participate in the FA–BRCA DNA repair pathway, a fundamental pathway in the development of the disease and the presentation of its characteristic symptoms. Certain symptoms such as oxygen sensitivity, hematological abnormalities and impaired immunity suggest that FA proteins could participate in or independently control other pathways as well. In this study, we identified 9 DNA repair genes that were down regulated in a genome wide analysis of 6 Indian Fanconi anemia patients. Functional clustering of a total of 233 dysregulated genes identified key biological processes that included regulation of transcription, DNA repair, cell cycle and chromosomal organization. Microarray data revealed the down regulation of ATXN3, ARID4A and ETS-1, which were validated by RTPCR in a subsequent sample set of 9 Indian FA patients. Here we report for the first time a gene expression profile of Fanconi anemia patients from the Indian population and a pool of genes that might aid in the acquisition and progression of the FA phenotype. [Copyright &y& Elsevier]

Abstract: Developmental Dyslexia (DD) is a heritable, complex genetic disorder characterized by specific impairment in reading and writing ability that is substantially below the expected reading ability given the person's chronological age, measured intelligence and age-appropriate education. More than ten susceptible genes have been identified for DD. A Single Nucleotide Polymorphism (SNP) of these genes was found to be associated with various phenotypes of DD. To identify the role of SNPs of four candidate genes namely, MRPL19/C2ORF3, ROBO1 and THEM2 in an Indian population, we genotyped eight SNPs of these genes in 157 children with DD and 212 normal readers using a MassARRAY technique with a MALDI-TOF MS analyzer. Power analysis of some of these SNPs showed >80% of power. Chi-square test, Odds Ratios (ORs), 95% Confidence Intervals (CIs) and Bonferroni's correction were applied to identify the significance of the genotyped SNPs and haplotypes. Our study failed to show any association of SNPs and haplotypes of these genes with DD in an Indian population. [Copyright &y& Elsevier]

Highlights: [•] First attempt from north India to dissect IL-17 axis in human tuberculosis (TB). [•] No association of IL17A and IL17F gene variants in pulmonary and extra-pulmonary TB [•] Correlated the serum cytokine levels and genotypes [•] IL17 variants might not be a major influencing gene for tuberculosis in north Indians. [ABSTRACT FROM AUTHOR]

Abstract: Santalum album L. commonly known as East-Indian sandal or chandan is a hemiparasitic tree of family santalaceae. Santalol is a bioprospecting molecule present in sandalwood and any effort towards metabolic engineering of this important moiety would require knowledge on gene regulation. Santalol is a sesquiterpene synthesized through mevalonate or non-mevalonate pathways. First step of santalol biosynthesis involves head to tail condensation of isopentenyl pyrophosphate (IPP) with its allylic co-substrate dimethyl allyl pyrophosphate (DMAPP) to produce geranyl pyrophosphate (GPP; C10 — a monoterpene). GPP upon one additional condensation with IPP produces farnesyl pyrophosphate (FPP; C15 — an open chain sesquiterpene). Both the reactions are catalyzed by farnesyl diphosphate synthase (FDS). Santalene synthase (SS), a terpene cyclase catalyzes cyclization of open ring FPP into a mixture of cyclic sesquiterpenes such as α-santalene, epi-β-santalene, β-santalene and exo bergamotene, the main constituents of sandal oil. The objective of the present work was to generate a comprehensive knowledge on the genes involved in santalol production and study their molecular regulation. To achieve this, sequences encoding farnesyl diphosphate synthase and santalene synthase were isolated from sandalwood using suppression subtraction hybridization and 2D gel electrophoresis technology. Functional characterization of both the genes was done through enzyme assays and tissue-specific expression of both the genes was studied. To our knowledge, this is the first report on studies on molecular regulation, and tissue-specific expression of the genes involved in santalol biosynthesis. [Copyright &y& Elsevier]

Abstract: hMLH1 is a member of mismatch repair genes (MMR) that plays a crucial role in correcting replication errors, cell cycle arrest, apoptosis and oxidative stress. We explored the risk associated with hMLH1 −93 A>G (rs 1800734) single nucleotide polymorphism (SNP) with the oral squamous cell carcinoma (OSCC) in Asian Indians. We genotyped 242 patients with tobacco-related OSCC and 205 healthy controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The frequency of AA genotype was found to be significantly (Pc <0.0006) lower in patients as compared to the controls (21.49% vs. 47.8%) while GG genotype showed significantly higher (Pc <0.0006) prevalence in patients as compared to the healthy controls (41.32% vs. 13.66%). In logistic regression analysis AG (adjusted OR=1.95, 95% CI=0.72–5.26) and GG genotype (adjusted OR=4.5, 95% CI=1.54–13.16, P =0.006) appeared susceptible when compared with the wild-type AA genotype. The allelic distribution showed that variant G allele is significantly higher (Pc <0.0004) in patients and associated with increased risk (adjusted OR=2.36, 95% CI=1.33–4.19, P =0.003) as compared to the wild-type A allele. Altogether, our results suggest that the hMLH1 −93 A>G polymorphism is associated with the higher risk of tobacco-related OSCC in Asian Indians and could be useful in screening population at a higher risk. [Copyright &y& Elsevier]

Abstract: Chewing betel quid may release chemical carcinogens including xenobiotics resulting in oral malignancy cases preceded by potential malignant lesions and conditions — Oral Submucous Fibrosis (OSF) being one of them. The cytochrome P4501A1 (CYP1A1) enzyme is central to the metabolic activation of these xenobiotics, whereas CYP2E1 metabolizes the nitrosamines and tannins. The present study investigated the association of polymorphisms at CYP1A1m1 (T3801C), m2 (A2455G), and CYP2E1 PstI site (nucleotide 21259) with the risk of OSF. The study was conducted on 75 OSF patients and 150 controls from an eastern Indian population. The above polymorphisms were analyzed by PCR-RFLP method. Analyses of data show that polymorphisms in CYP1A1m2 [OR=8.25 (4.31–15.80)]; CYP1A1m1 [OR=2.88 (1.57–5.24)] and CYP2E1 PstI site [OR=3.16 (1.10–9.04)] revealed significant association with OSF. Our results suggest that polymorphism in CYP1A1 and CYP2E1 may confer an increased risk for Oral Submucous Fibrosis. [Copyright &y& Elsevier]

Abstract: Background: Three mutations (two missense and one frameshift) in the NOD2 gene are associated with Crohn''s disease (CD) in a proportion of patients with Crohn''s disease in North America, Europe and Australia. These three mutations are not found in Indian patients with CD. We undertook new studies to identify polymorphisms in the NOD2 gene in the Indian population and to detect whether any of these were associated with inflammatory bowel disease (IBD) in this population. Methods: Individual exons of the NOD2 gene were amplified by PCR and subjected to denaturing high performance liquid chromatography (DHPLC) to detect heteroduplex formation. All 12 exons of the NOD2 gene were amplified and Sanger-sequenced to detect polymorphisms in the NOD2 gene. 310 patients with CD, 318 patients with ulcerative colitis (UC) and 442 healthy controls (HC) were recruited for association studies. DNA from these participants was evaluated for the identified eight polymorphisms by Sequenom analysis. Results: Heteroduplex formation was noted by DHPLC in exons 2 and 4 of the NOD2 gene. Sequencing of the entire NOD2 gene data revealed eight polymorphisms – rs2067085, rs2066842, rs2066843, rs1861759, rs2111235, rs5743266, rs2076753, and rs5743291 – of which the latter four were described for the first time in Indians. None of these polymorphisms was associated with CD. The SNPs rs2066842 and rs2066843 were in significant linkage disequilibrium. Both SNPs showed a significant association with UC (P=0.03 and 0.04 respectively; odds ratio 1.44 and 1.41 respectively). Conclusion: Four NOD2 polymorphisms were identified for the first time in the Indian population. Of 8 NOD2 polymorphisms, none were associated with CD but two were weakly associated with UC. NOD2 polymorphisms do not play a major role in CD genesis in India. [Copyright &y& Elsevier]

Abstract: Background: Genetics of non-alcoholic fatty liver (NAFLD) in Asian Indians has been inadequately studied. We investigated the association of polymorphisms C161T and Pro12Ala of peroxisome proliferator-activated receptor gamma (PPARγ) with clinical and biochemical parameters in Asian Indians with NAFLD. Methods: In this case–control study, 162 NAFLD cases and 173 controls were recruited. Abdominal ultrasound, clinical and biochemical profiles, fasting insulin levels and value of homeostasis model assessment of insulin resistance were determined. Polymerase chain reaction–restriction fragment length polymorphisms of two polymorphisms were performed. The association of these polymorphisms with clinical and biochemical parameters was analysed. Results: Higher frequency of Ala and T alleles of PPARγ was obtained in cases. Ala/Ala genotype of PPARγ (Pro12Ala) was associated with significantly higher serum triglycerides (TG), alkaline phosphatase (ALK) and waist–hip ratio in cases as compared to controls. In C161T polymorphism, TT genotype was significantly increased TG (p =0.04), total cholesterol (p =0.01), ALK (p =0.04) and gamma-glutamyl transpeptidase (p =0.007) in cases. The linkage disequilibrium for these two single-nucleotide polymorphisms of PPARγ was differed in cases (D1=0.1; p =0.006) and controls (D1=0.07; p =0.1). Using a multivariate analysis after adjusting for age, sex and body mass index, the presence of NAFLD was linked to these two polymorphisms (odds ratio 1.64 (95% CI: 1.09–2.45, p =0.05)]. Conclusion: Asian Indians in north India carrying the alleles Ala and T of PPARγ (Pro12Ala and C161T) polymorphisms are predisposed to develop NAFLD. [Copyright &y& Elsevier]

Abstract: India is a diverse land whose population holds the history of waves of human dispersal. Recent studies suggest two major ancestral contributions to most of the Indian sub-populations. However, present day Indians are thought to contain huge genetic diversity derived consequent to multiple cultural, linguistic and geographical variations. Genome-wide survey of individuals from current North (N-In) and South (S-In) India along with populations from HapMap Phase III and Indian sub-populations from HUGO Pan-Asian SNP Consortium is performed. Multivariate analysis (MDS and PCA) was carried out after merging data from the current study and other consortia. Indian sub-populations clustered separately from populations of major global geographical regions in MDS and PCA in a loose agglomeration except for two Indian subpopulations clustering near far eastern populations. Fst values indicated diversity among Indian sub-populations which was substantiated by STRUCTURE analysis suggesting the possibility of additional admixture events. [Copyright &y& Elsevier]

Abstract: Introduction: In view of the reported association of SNPs in the paraoxonase (PON1) gene with coronary artery disease (CAD), and the absence of conclusive data from India, we investigated the relationship of three SNPs at different loci (‐108C/T, L55M and Q192R) of the PON1 gene and their haplotypes with CAD among people residing in the northern plains of India. Materials and methods: One hundred and seventy-eight healthy controls and two hundred and four angiographically-proven CAD patients were genotyped using PCR-RFLP. Results: Of the three SNPs, only the R allele of Q192R polymorphism was associated with CAD (p<0.05). Two locus haplotypes QT (OR 0.55, p=0.0004, 95% CI 0.39–0.77, significant) and LQ (odds ratio 0.73, p=0.03, 95% CI 0.55–0.97, trend) showed protective effects, while haplotypes MR (OR=5.36, p=0.0001, 95% CI 2.045–14.049) and MC (OR=2.71, p=0.011, 95% CI 1.221–6.046) were associated with increased risk of CAD. MRT, a minor three-locus haplotype also displayed significant association (OR 4.93, 95% CI 1.7–13.5) with the disease. Significance was assessed after applying Bonferroni''s correction. Conclusions: Our study revealed that only one SNP at a single locus but several haplotype combinations of PON1 coding and promoter-region polymorphisms were associated with the risk of or protection against CAD. Thus, haplotype analysis brought better insights into the association of PON1 gene polymorphisms with CAD in Asian Indians. [Copyright &y& Elsevier]

Abstract: Bacterial artificial chromosomes (BACs) are used in genomic variation studies due to their capacity to carry a large insert, their high clonal stability, low rate of chimerism and ease of manipulation. In the present study, an attempt was made to create the first genomic BAC library of an anonymous Indian male (IMBL4) consisting of 100,224 clones covering the human genome more than three times. Restriction mapping of 255 BAC clones by pulse field gel electrophoresis confirmed an average insert size of 120kb. The library was screened by PCR using SHANK3 (SH3 and multiple ankyrin repeat domains 3) and OLFM3 (olfactomedin 3) specific primers. A selection of clones was analyzed by fluorescent in situ hybridization (FISH) and sequencing. Fine mapping of copy number variable regions by array based comparative genomic hybridization identified 467 CNVRs in the IMBL4 genome. The IMBL4 BAC library represents the first cataloged Indian genome resource for applications in basic and clinical research. [Copyright &y& Elsevier]

• Established the distribution of CYP2C19 variants in Indians using Infinium global screening array. • Five CYP2C19 variants were identified in Indians (*2 , *3 , *6 , *8 and *17) • The *2 and *17 variants are prevalent while *3, *6 and *8 are rare. • The *2 , *3 and *7 have lesser probability of exon skipping, while *17 has more probability. • In the presence of *17 variant, GATA1, MEF2 and EVI1 transcription factors binding is enhanced. • This increased binding contributes to DNA curvature in the presence of *17 variant. • The *5,*6, *8, *9 and *10 variants with higher evolutionary preservation are probably damaging. • Region-specific data of Indians clustered together except for Assamese. CYP2C19 metabolizes the antiplatelet and antiepileptic drugs. Any alteration in CYP2C19 activity might influence the therapeutic efficacy. The objective of this study was to identify CYP2C19 variants prevalent in Indians and perform their in silico characterization. Infinium global screening array (GSA) was used for CYP2C19 genotyping in 2000 healthy Indians. In addition, we performed in silico characterization of the identified variants. Out of the 11 variants covered (*2 , *3 , *4 , *5 , *6 , *7 , *8 , *9 , *10 , *11 , and *17), five were identified in Indians (*2 , *3 , *6 , *8 and *17). The *2 and *17 were the most prevalent alleles (minor allele frequencies, MAF: 32.0% and 13.95%). The *3 , *6 and *8 were rare (MAFs: 0.425%, 0.025% and 0.05%). The *2 variant is shown to affect the splicing at the fifth exon–intron boundary. The *3 variant is a non-sense variant that is predicted to be deleterious. On the otherhand, the *17 variant showed more binding affinity for GATA binding protein 1 (GATA1), myocyte enhancer factor 2 (MEF2) and ectotropic viral integration site 1 (EVI1). The *6 and *8 variants predicted to be deleterious. The *2 , *3 and *7 variants showed lesser probability of exon skipping, while *17 showed more probability. The genotype distribution of Indian subjects is comparable with that of South Asians (SAS) (1000 genome project, phase 3). The *2 , *3 and *17 variants are the key pharmacogenetic determinants in Indians. The *2 and *3 are loss-of-function variants. The *17 is a gain-of-function variant with increased binding of transcriptional factors. [ABSTRACT FROM AUTHOR]