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Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis

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Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. / Li, Zhixiu; Akar, Servet; Yarkan, Handan; Lee, Sau Kuen; Çetin, Pınar; Can, Gerçek; Kenar, Gökce; Çapa, Fernur; Pamuk, Omer Nuri; Pehlivan, Yavuz; Cremin, Katie; De Guzman, Erika; Harris, Jessica; Wheeler, Lawrie; Jamshidi, Ahmadreza; Vojdanian, Mahdi; Farhadi, Elham; Ahmadzadeh, Nooshin; Yüce, Zeynep; Dalkılıç, Ediz; Solmaz, Dilek; Akın, Berrin; Dönmez, Salim; Sarı, İsmail; Leo, Paul J.; Kenna, Tony J.; Önen, Fatos; Mahmoudi, Mahdi; Brown, Matthew A.; Akkoc, Nurullah; Masters, Seth Lucian (Editor).

In: PLoS Genetics, Vol. 15, No. 4, e1008038, 2019.

Research output: Contribution to journalArticle

Harvard

Li, Z, Akar, S, Yarkan, H, Lee, SK, Çetin, P, Can, G, Kenar, G, Çapa, F, Pamuk, ON, Pehlivan, Y, Cremin, K, De Guzman, E, Harris, J, Wheeler, L, Jamshidi, A, Vojdanian, M, Farhadi, E, Ahmadzadeh, N, Yüce, Z, Dalkılıç, E, Solmaz, D, Akın, B, Dönmez, S, Sarı, I, Leo, PJ, Kenna, TJ, Önen, F, Mahmoudi, M, Brown, MA, Akkoc, N & Masters, SL (ed.) 2019, 'Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis', PLoS Genetics, vol. 15, no. 4, e1008038. https://doi.org/10.1371/journal.pgen.1008038

APA

Li, Z., Akar, S., Yarkan, H., Lee, S. K., Çetin, P., Can, G., ... Masters, S. L. (Ed.) (2019). Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. PLoS Genetics, 15(4), [e1008038]. https://doi.org/10.1371/journal.pgen.1008038

Vancouver

Li Z, Akar S, Yarkan H, Lee SK, Çetin P, Can G et al. Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. PLoS Genetics. 2019;15(4). e1008038. https://doi.org/10.1371/journal.pgen.1008038

Author

Li, Zhixiu ; Akar, Servet ; Yarkan, Handan ; Lee, Sau Kuen ; Çetin, Pınar ; Can, Gerçek ; Kenar, Gökce ; Çapa, Fernur ; Pamuk, Omer Nuri ; Pehlivan, Yavuz ; Cremin, Katie ; De Guzman, Erika ; Harris, Jessica ; Wheeler, Lawrie ; Jamshidi, Ahmadreza ; Vojdanian, Mahdi ; Farhadi, Elham ; Ahmadzadeh, Nooshin ; Yüce, Zeynep ; Dalkılıç, Ediz ; Solmaz, Dilek ; Akın, Berrin ; Dönmez, Salim ; Sarı, İsmail ; Leo, Paul J. ; Kenna, Tony J. ; Önen, Fatos ; Mahmoudi, Mahdi ; Brown, Matthew A. ; Akkoc, Nurullah ; Masters, Seth Lucian (Editor). / Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis. In: PLoS Genetics. 2019 ; Vol. 15, No. 4.

Bibtex Download

@article{6a32618eab364e12b84d372d16dedabf,
title = "Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis",
abstract = "Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10−12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10−13). 99.6{\%} of Turkish AS cases, and 96{\%} of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10−15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10−8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.",
author = "Zhixiu Li and Servet Akar and Handan Yarkan and Lee, {Sau Kuen} and Pınar {\cC}etin and Ger{\cc}ek Can and G{\"o}kce Kenar and Fernur {\cC}apa and Pamuk, {Omer Nuri} and Yavuz Pehlivan and Katie Cremin and {De Guzman}, Erika and Jessica Harris and Lawrie Wheeler and Ahmadreza Jamshidi and Mahdi Vojdanian and Elham Farhadi and Nooshin Ahmadzadeh and Zeynep Y{\"u}ce and Ediz Dalkılı{\cc} and Dilek Solmaz and Berrin Akın and Salim D{\"o}nmez and İsmail Sarı and Leo, {Paul J.} and Kenna, {Tony J.} and Fatos {\"O}nen and Mahdi Mahmoudi and Brown, {Matthew A.} and Nurullah Akkoc and Masters, {Seth Lucian}",
year = "2019",
doi = "10.1371/journal.pgen.1008038",
language = "English",
volume = "15",
journal = "PL o S Genetics",
issn = "1553-7390",
number = "4",

}

RIS (suitable for import to EndNote) Download

TY - JOUR

T1 - Genome-wide association study in Turkish and Iranian populations identify rare familial Mediterranean fever gene (MEFV) polymorphisms associated with ankylosing spondylitis

AU - Li, Zhixiu

AU - Akar, Servet

AU - Yarkan, Handan

AU - Lee, Sau Kuen

AU - Çetin, Pınar

AU - Can, Gerçek

AU - Kenar, Gökce

AU - Çapa, Fernur

AU - Pamuk, Omer Nuri

AU - Pehlivan, Yavuz

AU - Cremin, Katie

AU - De Guzman, Erika

AU - Harris, Jessica

AU - Wheeler, Lawrie

AU - Jamshidi, Ahmadreza

AU - Vojdanian, Mahdi

AU - Farhadi, Elham

AU - Ahmadzadeh, Nooshin

AU - Yüce, Zeynep

AU - Dalkılıç, Ediz

AU - Solmaz, Dilek

AU - Akın, Berrin

AU - Dönmez, Salim

AU - Sarı, İsmail

AU - Leo, Paul J.

AU - Kenna, Tony J.

AU - Önen, Fatos

AU - Mahmoudi, Mahdi

AU - Brown, Matthew A.

AU - Akkoc, Nurullah

A2 - Masters, Seth Lucian

PY - 2019

Y1 - 2019

N2 - Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10−12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10−13). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10−15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10−8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

AB - Ankylosing spondylitis (AS) is a highly heritable immune-mediated arthritis common in Turkish and Iranian populations. Familial Mediterranean Fever (FMF) is an autosomal recessive autoinflammatory disease most common in people of Mediterranean origin. MEFV, an FMF-associated gene, is also a candidate gene for AS. We aimed to identify AS susceptibility loci and also examine the association between MEFV and AS in Turkish and Iranian cohorts. We performed genome-wide association studies in 1001 Turkish AS patients and 1011 Turkish controls, and 479 Iranian AS patients and 830 Iranian controls. Serum IL-1β, IL-17 and IL-23 cytokine levels were quantified in Turkish samples. An association of major effect was observed with a novel rare coding variant in MEFV in the Turkish cohort (rs61752717, M694V, OR = 5.3, P = 7.63×10−12), Iranian cohort (OR = 2.9, P = 0.042), and combined dataset (OR = 5.1, P = 1.65×10−13). 99.6% of Turkish AS cases, and 96% of those carrying MEFV rs61752717 variants, did not have FMF. In Turkish subjects, the association of rs61752717 was particularly strong in HLA-B27-negative cases (OR = 7.8, P = 8.93×10−15), but also positive in HLA-B27-positive cases (OR = 4.3, P = 7.69×10−8). Serum IL-1β, IL-17 and IL-23 levels were higher in AS cases than controls. Among AS cases, serum IL-1β and IL-23 levels were increased in MEFV 694V carriers compared with non-carriers. Our data suggest that FMF and AS have overlapping aetiopathogenic mechanisms. Functionally important MEFV mutations, such as M694V, lead to dysregulated inflammasome function and excessive IL-1β function. As IL-1 inhibition is effective in FMF, AS cases carrying FMF-associated MEFV variants may benefit from such therapy.

UR - http://www.scopus.com/inward/record.url?scp=85064997427&partnerID=8YFLogxK

U2 - 10.1371/journal.pgen.1008038

DO - 10.1371/journal.pgen.1008038

M3 - Article

VL - 15

JO - PL o S Genetics

JF - PL o S Genetics

SN - 1553-7390

IS - 4

M1 - e1008038

ER -

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