Title |
A Coding Variant of ANO10, Affecting Volume Regulation of Macrophages, Is Associated with Borrelia Seropositivity
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Published in |
Molecular Medicine, February 2015
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DOI | 10.2119/molmed.2014.00219 |
Pubmed ID | |
Authors |
Christian Hammer, Podchanart Wanitchakool, Lalida Sirianant, Sergi Papiol, Mathieu Monnheimer, Diana Faria, Jiraporn Ousingsawat, Natalie Schramek, Corinna Schmitt, Gabriele Margos, Angelika Michel, Peter Kraiczy, Michael Pawlita, Rainer Schreiber, Thomas F. Schulz, Volker Fingerle, Hayrettin Tumani, Hannelore Ehrenreich, Karl Kunzelmann |
Abstract |
In a first genome-wide association study (GWAS) approach to anti-Borrelia seropositivity, we identified two significant single nucleotide polymorphisms (SNP) (rs17850869, P=4.17E-09; rs41289586, P=7.18E-08). Both markers, located on chromosomes 16 and 3, respectively, are within or close to genes previously connected to spinocerebellar ataxia. The risk SNP rs41289586 represents a missense variant (R263H) of anoctamin10 (ANO10), a member of a protein family encoding Cl(-) channels and phospholipid scramblases. ANO10 augments volume regulated Cl(-) currents (IHypo) in Xenopus oocytes, HEK293 cells, lymphocytes and macrophages and controls volume regulation by enhancing regulatory volume decrease (RVD). ANO10 supports migration of macrophages, and phagocytosis of spirochetes. The R263H variant is inhibitory on IHypo, RVD and intracellular Ca(2+) signals, which may delay spirochete clearance, thereby sensitizing adaptive immunity. Our data demonstrate for the first time that ANO10 has a central role in innate immune defense against Borrelia infection. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 20% |
Unknown | 4 | 80% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 4 | 80% |
Practitioners (doctors, other healthcare professionals) | 1 | 20% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Germany | 2 | 4% |
Unknown | 47 | 96% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 7 | 14% |
Researcher | 6 | 12% |
Professor | 5 | 10% |
Student > Doctoral Student | 4 | 8% |
Student > Master | 4 | 8% |
Other | 8 | 16% |
Unknown | 15 | 31% |
Readers by discipline | Count | As % |
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Neuroscience | 8 | 16% |
Immunology and Microbiology | 5 | 10% |
Biochemistry, Genetics and Molecular Biology | 4 | 8% |
Medicine and Dentistry | 3 | 6% |
Agricultural and Biological Sciences | 3 | 6% |
Other | 7 | 14% |
Unknown | 19 | 39% |