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Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study

Reiman, Eric M. ; Arboleda-Velasquez, Joseph F. ; Quiroz, Yakeel T. ; [et al.]

Springer Science and Business Media LLC ; 2020

In: Nature Communications Vol. 11, No. 1 ( 2020-02-03)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 11, No. 1 ( 2020-02-03)

Abstract: Each additional copy of the apolipoprotein E4 (APOE4) allele is associated with a higher risk of Alzheimer’s dementia, while the APOE2 allele is associated with a lower risk of Alzheimer’s dementia, it is not yet known whether APOE2 homozygotes have a particularly low risk. We generated Alzheimer’s dementia odds ratios and other findings in more than 5,000 clinically characterized and neuropathologically characterized Alzheimer’s dementia cases and controls. APOE2/2 was associated with a low Alzheimer’s dementia odds ratios compared to APOE2/3 and 3/3, and an exceptionally low odds ratio compared to APOE4/4, and the impact of APOE2 and APOE4 gene dose was significantly greater in the neuropathologically confirmed group than in more than 24,000 neuropathologically unconfirmed cases and controls. Finding and targeting the factors by which APOE and its variants influence Alzheimer’s disease could have a major impact on the understanding, treatment and prevention of the disease.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/s41467-019-14279-8

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2553671-0

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LATE-NC risk alleles (in TMEM106B, GRN, and ABCC9 genes) among persons with African ancestry

Katsumata, Yuriko ; Fardo, David W ; Shade, Lincoln M P ; [et al.]

Oxford University Press (OUP) ; 2023

In: Journal of Neuropathology & Experimental Neurology Vol. 82, No. 9 ( 2023-08-21), p. 760-768

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In: Journal of Neuropathology & Experimental Neurology, Oxford University Press (OUP), Vol. 82, No. 9 ( 2023-08-21), p. 760-768

Type of Medium: Online Resource

ISSN: 0022-3069

URL: Article

DOI: 10.1093/jnen/nlad059

RVK:

XA 55250

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2023

detail.hit.zdb_id: 2033048-0

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Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Wain, Louise V ; Understanding Society Scientific Group ; Shrine, Nick ; [et al.]

Springer Science and Business Media LLC ; 2017

In: Nature Genetics Vol. 49, No. 3 ( 2017-3), p. 416-425

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In: Nature Genetics, Springer Science and Business Media LLC, Vol. 49, No. 3 ( 2017-3), p. 416-425

Type of Medium: Online Resource

ISSN: 1061-4036 , 1546-1718

URL: Article

DOI: 10.1038/ng.3787

RVK:

XA 10000

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 1494946-5

SSG: 12

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GSTCD and INTS12 Regulation and Expression in the Human Lung

Obeidat, Ma’en ; Miller, Suzanne ; Probert, Kelly ; [et al.]

Public Library of Science (PLoS) ; 2013

In: PLoS ONE Vol. 8, No. 9 ( 2013-9-18), p. e74630-

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In: PLoS ONE, Public Library of Science (PLoS), Vol. 8, No. 9 ( 2013-9-18), p. e74630-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0074630

DOI: 10.1371/journal.pone.0074630.g001

DOI: 10.1371/journal.pone.0074630.g002

DOI: 10.1371/journal.pone.0074630.g003

DOI: 10.1371/journal.pone.0074630.g004

DOI: 10.1371/journal.pone.0074630.g005

DOI: 10.1371/journal.pone.0074630.g006

DOI: 10.1371/journal.pone.0074630.t001

DOI: 10.1371/journal.pone.0074630.t002

DOI: 10.1371/journal.pone.0074630.t003

DOI: 10.1371/journal.pone.0074630.s001

DOI: 10.1371/journal.pone.0074630.s002

DOI: 10.1371/journal.pone.0074630.s003

DOI: 10.1371/journal.pone.0074630.s004

DOI: 10.1371/journal.pone.0074630.s005

DOI: 10.1371/journal.pone.0074630.s006

DOI: 10.1371/journal.pone.0074630.s007

DOI: 10.1371/journal.pone.0074630.s008

DOI: 10.1371/journal.pone.0074630.s009

DOI: 10.1371/journal.pone.0074630.s010

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2013

detail.hit.zdb_id: 2267670-3

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The Ser82 RAGE Variant Affects Lung Function and Serum RAGE in Smokers and sRAGE Production In Vitro

Miller, Suzanne ; Henry, Amanda P. ; Hodge, Emily ; [et al.]

Public Library of Science (PLoS) ; 2016

In: PLOS ONE Vol. 11, No. 10 ( 2016-10-18), p. e0164041-

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In: PLOS ONE, Public Library of Science (PLoS), Vol. 11, No. 10 ( 2016-10-18), p. e0164041-

Type of Medium: Online Resource

ISSN: 1932-6203

URL: Article

DOI: 10.1371/journal.pone.0164041

DOI: 10.1371/journal.pone.0164041.g001

DOI: 10.1371/journal.pone.0164041.g002

DOI: 10.1371/journal.pone.0164041.g003

DOI: 10.1371/journal.pone.0164041.g004

DOI: 10.1371/journal.pone.0164041.g005

DOI: 10.1371/journal.pone.0164041.g006

DOI: 10.1371/journal.pone.0164041.t001

DOI: 10.1371/journal.pone.0164041.t002

DOI: 10.1371/journal.pone.0164041.s001

DOI: 10.1371/journal.pone.0164041.s002

DOI: 10.1371/journal.pone.0164041.s003

Language: English

Publisher: Public Library of Science (PLoS)

Publication Date: 2016

detail.hit.zdb_id: 2267670-3

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HTR4 gene structure and altered expression in the developing lung

Hodge, Emily ; Nelson, Carl P ; Miller, Suzanne ; [et al.]

Springer Science and Business Media LLC ; 2013

In: Respiratory Research Vol. 14, No. 1 ( 2013-12)

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In: Respiratory Research, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2013-12)

Abstract: Meta-analyses of genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) spanning the 5-hydroxytryptamine receptor 4 (5-HT 4 R) gene ( HTR4 ) associated with lung function. The aims of this study were to i) investigate the expression profile of HTR4 in adult and fetal lung tissue and cultured airway cells, ii) further define HTR4 gene structure and iii) explore the potential functional implications of key SNPs using a bioinformatic approach. Methods Following reverse transcription (RT)-PCR in human brain, 5′ rapid amplification of cDNA ends (5′ RACE) was used to examine the exonic structure of HTR4 at the 5′ end. Quantitative (Q)-PCR was used to quantify HTR4 mRNA expression in total RNA from cultured airway cells and whole lung tissue. Publically available gene microarray data on fetal samples of estimated gestational age 7–22 weeks were mined for HTR4 expression. Immunohistochemistry (IHC; in adult and fetal lung tissue) and a radioligand binding assay (in cultured airway cells) were used to analyze 5HT 4 R protein expression. Results IHC in adult lung, irrespective of the presence of chronic obstructive pulmonary disease (COPD), suggested low level expression of 5-HT 4 R protein, which was most prominent in alveolar pneumocytes. There was evidence of differential 5-HT 4 R protein levels during gestation in fetal lung, which was also evident in gene expression microarray data. HTR4 mRNA expression, assessed by Q-PCR, was 〈 0.5% relative to brain in total adult lung tissue and in human airway smooth muscle (HASM) and bronchial epithelial cells (HBEC) derived from adult donors. Radioligand binding experiments also indicated that HBEC and HASM cells did not express a significant 5-HT 4 R population. 5′ RACE in brain identified a novel N -terminal variant, containing an extended N- terminal sequence. The functional significance of key HTR4 SNPs was investigated using the encyclopedia of DNA elements consortium (ENCODE) dataset. These analyses identified multiple alterations in regulatory motifs for transcription factors implicated in lung development, including Foxp1. Conclusions Taken together, these data suggest a role for HTR4 in lung development, which may at least in part explain the genetic association with lung function.

Type of Medium: Online Resource

ISSN: 1465-993X

URL: Article

DOI: 10.1186/1465-9921-14-77

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2013

detail.hit.zdb_id: 2041675-1

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Genome-Wide Association Studies Identify CHRNA5/3 and HTR4 in the Development of Airflow Obstruction

Wilk, Jemma B. ; Shrine, Nick R. G. ; Loehr, Laura R. ; [et al.]

American Thoracic Society ; 2012

In: American Journal of Respiratory and Critical Care Medicine Vol. 186, No. 7 ( 2012-10-01), p. 622-632

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In: American Journal of Respiratory and Critical Care Medicine, American Thoracic Society, Vol. 186, No. 7 ( 2012-10-01), p. 622-632

Type of Medium: Online Resource

ISSN: 1073-449X , 1535-4970

URL: Article

DOI: 10.1164/rccm.201202-0366OC

RVK:

XA 21200

Language: English

Publisher: American Thoracic Society

Publication Date: 2012

detail.hit.zdb_id: 1468352-0

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Defining a role for lung function associated gene GSTCD in cell homeostasis

Henry, Amanda P. ; Probert, Kelly ; Stewart, Ceri E. ; [et al.]

Springer Science and Business Media LLC ; 2019

In: Respiratory Research Vol. 20, No. 1 ( 2019-12)

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In: Respiratory Research, Springer Science and Business Media LLC, Vol. 20, No. 1 ( 2019-12)

Type of Medium: Online Resource

ISSN: 1465-993X

URL: Article

DOI: 10.1186/s12931-019-1146-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2019

detail.hit.zdb_id: 2041675-1

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Proinflammatory Effects in Ex Vivo Human Lung Tissue of Respirable Smoke Extracts from Indoor Cooking in Nepal

KC, Binaya ; Mahapatra, Parth Sarathi ; Thakker, Dhruma ; [et al.]

American Thoracic Society ; 2020

In: Annals of the American Thoracic Society Vol. 17, No. 6 ( 2020-06), p. 688-698

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In: Annals of the American Thoracic Society, American Thoracic Society, Vol. 17, No. 6 ( 2020-06), p. 688-698

Type of Medium: Online Resource

ISSN: 2329-6933 , 2325-6621

URL: Article

DOI: 10.1513/AnnalsATS.201911-827OC

Language: English

Publisher: American Thoracic Society

Publication Date: 2020

detail.hit.zdb_id: 2702474-X

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Chloride intracellular channel 1 (CLIC1) contributes to modulation of cyclic AMP-activated whole-cell chloride currents in human bronchial epithelial cells

Liu, Bo ; Billington, Charlotte K. ; Henry, Amanda P. ; [et al.]

Wiley ; 2018

In: Physiological Reports Vol. 6, No. 2 ( 2018-01), p. e13508-

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In: Physiological Reports, Wiley, Vol. 6, No. 2 ( 2018-01), p. e13508-

Type of Medium: Online Resource

ISSN: 2051-817X

URL: Article

DOI: 10.14814/phy2.13508

Language: English

Publisher: Wiley

Publication Date: 2018

detail.hit.zdb_id: 2724325-4

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