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5 results on '"Kanchan, Kanika"'

1. HLA-associated outcomes in peanut oral immunotherapy trials identify mechanistic and clinical determinants of therapeutic success.

Author

Kanchan, Kanika, Shankar, Gautam, Huffaker, Michelle F, Bahnson, Henry T, Chinthrajah, R Sharon, Sanda, Srinath, Manohar, Monali, Ling, Hua, Paschall, Justin E, Toit, George Du, Ruczinski, Ingo, Togias, Alkis, Lack, Gideon, Nadeau, Kari C, Jones, Stacie M, Nepom, Gerald T, and Mathias, Rasika A

Subjects
Humans, Peanut Hypersensitivity, Immunoglobulin G, Immunologic Factors, Immunotherapy, Adolescent, Adult, Middle Aged, Child, Clinical Trials as Topic, Young Adult, Arachis, HLA, desensitization, oral immunotherapy, peanut allergy, remission, tolerance, Clinical Research, Genetics, Prevention, Human Genome, Good Health and Well Being, Immunology, Medical Microbiology
Abstract

RationalePrevious studies identified an interaction between HLA and oral peanut exposure. HLA-DQA1*01:02 had a protective role with the induction of Ara h 2 epitope-specific IgG4 associated with peanut consumption during the LEAP clinical trial for prevention of peanut allergy, while it was a risk allele for peanut allergy in the peanut avoidance group. We have now evaluated this gene-environment interaction in two subsequent peanut oral immunotherapy (OIT) trials - IMPACT and POISED - to better understand the potential for the HLA-DQA1*01:02 allele as an indicator of higher likelihood of desensitization, sustained unresponsiveness, and peanut allergy remission.MethodsWe determined HLA-DQA1*01:02 carrier status using genome sequencing from POISED (N=118, age: 7-55yr) and IMPACT (N=126, age: 12-

Published
2022

2. Genome sequencing unveils a regulatory landscape of platelet reactivity.

Author

Keramati, Ali R, Chen, Ming-Huei, Rodriguez, Benjamin AT, Yanek, Lisa R, Bhan, Arunoday, Gaynor, Brady J, Ryan, Kathleen, Brody, Jennifer A, Zhong, Xue, Wei, Qiang, NHLBI Trans-Omics for Precision (TOPMed) Consortium, Kammers, Kai, Kanchan, Kanika, Iyer, Kruthika, Kowalski, Madeline H, Pitsillides, Achilleas N, Cupples, L Adrienne, Li, Bingshan, Schlaeger, Thorsten M, Shuldiner, Alan R, O'Connell, Jeffrey R, Ruczinski, Ingo, Mitchell, Braxton D, Faraday, Nauder, Taub, Margaret A, Becker, Lewis C, Lewis, Joshua P, Mathias, Rasika A, and Johnson, Andrew D

Subjects
NHLBI Trans-Omics for Precision (TOPMed) Consortium, Blood Platelets, K562 Cells, Humans, Thrombosis, GTP-Binding Proteins, RGS Proteins, Receptors, Cell Surface, Platelet Function Tests, Chromosome Mapping, Base Sequence, Platelet Aggregation, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study, HEK293 Cells, Whole Genome Sequencing
Abstract

Platelet aggregation at the site of atherosclerotic vascular injury is the underlying pathophysiology of myocardial infarction and stroke. To build upon prior GWAS, here we report on 16 loci identified through a whole genome sequencing (WGS) approach in 3,855 NHLBI Trans-Omics for Precision Medicine (TOPMed) participants deeply phenotyped for platelet aggregation. We identify the RGS18 locus, which encodes a myeloerythroid lineage-specific regulator of G-protein signaling that co-localizes with expression quantitative trait loci (eQTL) signatures for RGS18 expression in platelets. Gene-based approaches implicate the SVEP1 gene, a known contributor of coronary artery disease risk. Sentinel variants at RGS18 and PEAR1 are associated with thrombosis risk and increased gastrointestinal bleeding risk, respectively. Our WGS findings add to previously identified GWAS loci, provide insights regarding the mechanism(s) by which genetics may influence cardiovascular disease risk, and underscore the importance of rare variant and regulatory approaches to identifying loci contributing to complex phenotypes.

Published
2021

3. Genomic integrity of human induced pluripotent stem cells across nine studies in the NHLBI NextGen program

Author

Kanchan, Kanika, Iyer, Kruthika, Yanek, Lisa R, Carcamo-Orive, Ivan, Taub, Margaret A, Malley, Claire, Baldwin, Kristin, Becker, Lewis C, Broeckel, Ulrich, Cheng, Linzhao, Cowan, Chad, D'Antonio, Matteo, Frazer, Kelly A, Quertermous, Thomas, Mostoslavsky, Gustavo, Murphy, George, Rabinovitch, Marlene, Rader, Daniel J, Steinberg, Martin H, Topol, Eric, Yang, Wenli, Knowles, Joshua W, Jaquish, Cashell E, Ruczinski, Ingo, and Mathias, Rasika A

Subjects
Biological Sciences, Genetics, Stem Cell Research - Induced Pluripotent Stem Cell - Human, Stem Cell Research - Induced Pluripotent Stem Cell, Biotechnology, Human Genome, Cancer, Stem Cell Research, 2.1 Biological and endogenous factors, Aetiology, Cell Differentiation, DNA Copy Number Variations, DNA-Binding Proteins, Genomic Instability, Genomics, Humans, Induced Pluripotent Stem Cells, National Heart, Lung, and Blood Institute (U.S.), United States, hiPSCs, Structural integrity, GWAS, VanillaICE, Oncogenes, Tumor suppressor genes, Medical and Health Sciences, Developmental Biology, Medical biotechnology, Oncology and carcinogenesis
Abstract

Human induced pluripotent stem cell (hiPSC) lines have previously been generated through the NHLBI sponsored NextGen program at nine individual study sites. Here, we examined the structural integrity of 506 hiPSC lines as determined by copy number variations (CNVs). We observed that 149 hiPSC lines acquired 258 CNVs relative to donor DNA. We identified six recurrent regions of CNVs on chromosomes 1, 2, 3, 16 and 20 that overlapped with cancer associated genes. Furthermore, the genes mapping to regions of acquired CNVs show an enrichment in cancer related biological processes (IL6 production) and signaling cascades (JNK cascade & NFκB cascade). The genomic region of instability on chr20 (chr20q11.2) includes transcriptomic signatures for cancer associated genes such as ID1, BCL2L1, TPX2, PDRG1 and HCK. Of these HCK shows statistically significant differential expression between carrier and non-carrier hiPSC lines. Overall, while a low level of genomic instability was observed in the NextGen generated hiPSC lines, the observation of structural instability in regions with known cancer associated genes substantiates the importance of systematic evaluation of genetic variations in hiPSCs before using them as disease/research models.

Published
2020

4. NEGATIVE EPISTASIS BETWEEN α+ THALASSAEMIA AND SICKLE CELL TRAIT CAN EXPLAIN INTERPOPULATION VARIATION IN SOUTH ASIA

Author

Penman, Bridget S, Habib, Saman, Kanchan, Kanika, Gupta, Sunetra, and Read, A

Subjects
congenital, hereditary, and neonatal diseases and abnormalities, Asia, malaria, population genetics, Epistasis, Genetic, South Asia, Brief Communication, Biological Evolution, Sickle Cell Trait, sickle cell, human evolution, alpha-Thalassemia, hemic and lymphatic diseases, parasitic diseases, Epistasis, Humans, Selection, Genetic, Disease Resistance
Abstract

Recent studies in Kenya and Ghana have shown that individuals who inherit two malaria-protective genetic disorders of haemoglobin-α(+) thalassaemia and sickle cell trait-experience a much lower level of malaria protection than those who inherit sickle cell trait alone. We have previously demonstrated that this can limit the frequency of α(+) thalassaemia in a population in which sickle cell is present, which may account for the frequency of α(+) thalassaemia in sub-Saharan Africa not exceeding 50%. Here we consider the relationship between α(+) thalassaemia and sickle cell in South Asian populations, and show that very high levels of α(+) thalassaemia combined with varying levels of malaria selection can explain why sickle cell has penetrated certain South Asian populations but not others.

Published
2011

5. Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

Author

Sinha, Swapnil, Qidwai, Tabish, Kanchan, Kanika, Anand, Prerna, Jha, Ganga N, Pati, Sudhanshu S, Mohanty, Sanjib, Mishra, Saroj K, Tyagi, Prajesh K, Sharma, Surya K, Consortium, Indian Genome Variation, Venkatesh, Vimala, and Habib, Saman

Subjects
CD36 Antigens, Linkage disequilibrium, lcsh:Arctic medicine. Tropical medicine, Haploview, lcsh:RC955-962, Population, Plasmodium falciparum, India, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, lcsh:Infectious and parasitic diseases, Host-Parasite Interactions, Gene Frequency, parasitic diseases, Animals, Humans, lcsh:RC109-216, Genetic Predisposition to Disease, Allele, Malaria, Falciparum, education, Allele frequency, Alleles, Genetics, education.field_of_study, biology, Research, biology.organism_classification, Intercellular Adhesion Molecule-1, Minor allele frequency, Platelet Endothelial Cell Adhesion Molecule-1, Infectious Diseases, Case-Control Studies, Immunology, Parasitology
Abstract

BackgroundHost adhesion molecules play a significant role in the pathogenesis ofPlasmodium falciparummalaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes,ICAM1,PECAM1andCD36, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.MethodsThe frequency distribution of seven selected SNPs ofICAM1,PECAM1andCD36was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.ResultsAssociation of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of thePECAM1gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.ConclusionThe data highlights the significance of variations in theICAM1,PECAM1andCD36genes in the manifestation of falciparum malaria in India. ThePECAM1exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.

Published
2008

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