DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria

Anne Catrin Uhlemann; Nicole A. Szlezák; Reinhard Vonthein; Jürgen Tomiuk; Stefanie A. Emmer; Bertrand Lell; Peter G. Kremsner; Jürgen F.J. Kun

doi:10.1086/421242

DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91^phox subunit of NADPH oxidase and mediates protection against severe malaria

Anne Catrin Uhlemann^*, Nicole A. Szlezák, Reinhard Vonthein, Jürgen Tomiuk, Stefanie A. Emmer, Bertrand Lell, Peter G. Kremsner, Jürgen F.J. Kun

^*Corresponding author for this work

Institute of Medical Biometry and Statistic

29 Citations (Scopus)

Abstract

Reactive oxygen intermediates (ROIs) play a major role in the nonspecific innate immune response to invading microorganisms, such as Plasmodium falciparum. In a search for genetic markers that determine differences in production of ROI, we detected a highly polymorphic region of dinucleotide TA repeats ∼550 bp upstream of the NADPH oxidase gp91^phox subunit promoter. We genotyped 183 matched Gabonese children with severe or mild malaria. Repeat lengths TA₁₁ and TA₁₆ differed significantly in frequency between mild and severe infection, which suggests protection against severe malaria. Both repeat lengths showed lower levels of NADPH oxidase and promoter activities, which can be explained by a cyclic trend in TA repeat length with a period of ∼5, which indicates the necessity of correct DNA phasing between 2 possible control regions in the promoter. We provide a molecular model of how DNA phasing generated by TA dinucleotide polymorphisms may influence the expression level and protect against severe malaria.

Original language	English
Journal	Journal of Infectious Diseases
Volume	189
Issue number	12
Pages (from-to)	2227-2234
Number of pages	8
ISSN	0022-1899
DOIs	https://doi.org/10.1086/421242
Publication status	Published - 15.06.2004

Funding

Received 28 August 2003; accepted 20 December 2003; electronically published 25 May 2004. Financial support: Bundesministerium für Bildung und Forschung (grant 01GS0114 to J.F.J.K., as a member of the National Genome Research Network). a Present affiliation: Department of Infectious Diseases, St. George’s Hospital Medical School, London, United Kingdom. Reprints or correspondence: Anne-Catrin Uhlemann, St. George’s Hospital Medical School, Cranmer Terrace, SW17 ORE, London, UK (a.uhlemann@sghms .ac.uk).

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1086/421242

Cite this

Uhlemann, A. C., Szlezák, N. A., Vonthein, R., Tomiuk, J., Emmer, S. A., Lell, B., Kremsner, P. G., & Kun, J. F. J. (2004). DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91^phox subunit of NADPH oxidase and mediates protection against severe malaria. Journal of Infectious Diseases, 189(12), 2227-2234. https://doi.org/10.1086/421242

@article{7e47da07356d4d1d95570fc4ddcdc95f,

title = "DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria",

abstract = "Reactive oxygen intermediates (ROIs) play a major role in the nonspecific innate immune response to invading microorganisms, such as Plasmodium falciparum. In a search for genetic markers that determine differences in production of ROI, we detected a highly polymorphic region of dinucleotide TA repeats ∼550 bp upstream of the NADPH oxidase gp91phox subunit promoter. We genotyped 183 matched Gabonese children with severe or mild malaria. Repeat lengths TA11 and TA16 differed significantly in frequency between mild and severe infection, which suggests protection against severe malaria. Both repeat lengths showed lower levels of NADPH oxidase and promoter activities, which can be explained by a cyclic trend in TA repeat length with a period of ∼5, which indicates the necessity of correct DNA phasing between 2 possible control regions in the promoter. We provide a molecular model of how DNA phasing generated by TA dinucleotide polymorphisms may influence the expression level and protect against severe malaria.",

author = "Uhlemann, \{Anne Catrin\} and Szlez{\'a}k, \{Nicole A.\} and Reinhard Vonthein and J{\"u}rgen Tomiuk and Emmer, \{Stefanie A.\} and Bertrand Lell and Kremsner, \{Peter G.\} and Kun, \{J{\"u}rgen F.J.\}",

note = "Funding Information: Received 28 August 2003; accepted 20 December 2003; electronically published 25 May 2004. Financial support: Bundesministerium f{\"u}r Bildung und Forschung (grant 01GS0114 to J.F.J.K., as a member of the National Genome Research Network). a Present affiliation: Department of Infectious Diseases, St. George{\textquoteright}s Hospital Medical School, London, United Kingdom. Reprints or correspondence: Anne-Catrin Uhlemann, St. George{\textquoteright}s Hospital Medical School, Cranmer Terrace, SW17 ORE, London, UK (a.uhlemann@sghms .ac.uk).",

year = "2004",

month = jun,

day = "15",

doi = "10.1086/421242",

language = "English",

volume = "189",

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Uhlemann, AC, Szlezák, NA, Vonthein, R, Tomiuk, J, Emmer, SA, Lell, B, Kremsner, PG & Kun, JFJ 2004, 'DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91^phox subunit of NADPH oxidase and mediates protection against severe malaria', Journal of Infectious Diseases, vol. 189, no. 12, pp. 2227-2234. https://doi.org/10.1086/421242

DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91^phox subunit of NADPH oxidase and mediates protection against severe malaria. / Uhlemann, Anne Catrin; Szlezák, Nicole A.; Vonthein, Reinhard et al.
In: Journal of Infectious Diseases, Vol. 189, No. 12, 15.06.2004, p. 2227-2234.

Research output: Journal Articles › Journal articles › Research › peer-review

TY - JOUR

T1 - DNA phasing by TA dinucleotide microsatellite length determines in vitro and in vivo expression of the gp91phox subunit of NADPH oxidase and mediates protection against severe malaria

AU - Uhlemann, Anne Catrin

AU - Szlezák, Nicole A.

AU - Vonthein, Reinhard

AU - Tomiuk, Jürgen

AU - Emmer, Stefanie A.

AU - Lell, Bertrand

AU - Kremsner, Peter G.

AU - Kun, Jürgen F.J.

N1 - Funding Information: Received 28 August 2003; accepted 20 December 2003; electronically published 25 May 2004. Financial support: Bundesministerium für Bildung und Forschung (grant 01GS0114 to J.F.J.K., as a member of the National Genome Research Network). a Present affiliation: Department of Infectious Diseases, St. George’s Hospital Medical School, London, United Kingdom. Reprints or correspondence: Anne-Catrin Uhlemann, St. George’s Hospital Medical School, Cranmer Terrace, SW17 ORE, London, UK (a.uhlemann@sghms .ac.uk).

PY - 2004/6/15

Y1 - 2004/6/15

N2 - Reactive oxygen intermediates (ROIs) play a major role in the nonspecific innate immune response to invading microorganisms, such as Plasmodium falciparum. In a search for genetic markers that determine differences in production of ROI, we detected a highly polymorphic region of dinucleotide TA repeats ∼550 bp upstream of the NADPH oxidase gp91phox subunit promoter. We genotyped 183 matched Gabonese children with severe or mild malaria. Repeat lengths TA11 and TA16 differed significantly in frequency between mild and severe infection, which suggests protection against severe malaria. Both repeat lengths showed lower levels of NADPH oxidase and promoter activities, which can be explained by a cyclic trend in TA repeat length with a period of ∼5, which indicates the necessity of correct DNA phasing between 2 possible control regions in the promoter. We provide a molecular model of how DNA phasing generated by TA dinucleotide polymorphisms may influence the expression level and protect against severe malaria.

AB - Reactive oxygen intermediates (ROIs) play a major role in the nonspecific innate immune response to invading microorganisms, such as Plasmodium falciparum. In a search for genetic markers that determine differences in production of ROI, we detected a highly polymorphic region of dinucleotide TA repeats ∼550 bp upstream of the NADPH oxidase gp91phox subunit promoter. We genotyped 183 matched Gabonese children with severe or mild malaria. Repeat lengths TA11 and TA16 differed significantly in frequency between mild and severe infection, which suggests protection against severe malaria. Both repeat lengths showed lower levels of NADPH oxidase and promoter activities, which can be explained by a cyclic trend in TA repeat length with a period of ∼5, which indicates the necessity of correct DNA phasing between 2 possible control regions in the promoter. We provide a molecular model of how DNA phasing generated by TA dinucleotide polymorphisms may influence the expression level and protect against severe malaria.

UR - https://www.scopus.com/pages/publications/2942555351

U2 - 10.1086/421242

DO - 10.1086/421242

M3 - Journal articles

C2 - 15181570

AN - SCOPUS:2942555351

SN - 0022-1899

VL - 189

SP - 2227

EP - 2234

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

IS - 12

ER -