The Involvement of ALPK3 in Hypertrophic Cardiomyopathy in East Asia

被引：9

作者：

Dai, Jiaqi ^{[1
,2
]}

Li, Ke ^{[2
]}

Huang, Man ^{[2
]}

Sun, Yang ^{[1
,2
]}

Liu, Hao ^{[2
]}

Li, Zongzhe ^{[1
,2
]}

Chen, Peng ^{[1
,2
]}

Wang, Hong ^{[1
]}

Wu, Dongyang ^{[2
]}

Chen, Yanghui ^{[2
]}

Xiao, Lei ^{[2
]}

Wei, Haoran ^{[2
]}

Li, Rui ^{[1
,2
]}

Peng, Liyuan ^{[1
]}

Yu, Ting ^{[1
]}

Wang, Yan ^{[1
,2
]}

Wang, Dao Wen ^{[1
,2
]}

机构：

[1] Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Coll, Dept Internal Med, Wuhan, Peoples R China

[2] Huazhong Univ Sci & Technol, Hubei Key Lab Genet & Mol Mech Cardiol Disorders, Wuhan, Peoples R China

来源：

FRONTIERS IN MEDICINE | 2022年 / 9卷

基金：

中国国家自然科学基金;

关键词：

hypertrophic cardiomyopathy; East Asians; ALPK3; heterozygote; missense variant; VARIANTS; RISK;

D O I：

10.3389/fmed.2022.915649

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

ObjectiveALPK3 is associated with a recessive form of pediatric cardiomyopathy accompanied by musculoskeletal and craniofacial abnormalities. Heterozygous truncating variants in this gene (ALPK3tv) have recently been confirmed as a cause of autosomal dominant hypertrophic cardiomyopathy (HCM). Whether ALPK3 is also implicated in HCM in East Asia and the effect of missense variants in ALPK3 on HCM remains unresolved. MethodsWe compared the frequency of rare deleterious variants in ALPK3 in a study cohort comprised of 793 HCM cases of East Asian descent to that in the controls subset of Genome Aggregation Database (gnomAD). Gene burden test was used to assess this association. The involvement of these variants in HCM was further validated by independent cohort. The clinical characteristics and prognoses of these carriers were compared with sarcomere-positive and negative patients. ResultsRare deleterious variants in ALPK3 were significantly enriched in HCM compared with gnomAD controls (truncating: 4/793 vs. 4/4523, P = 0.02; missense: 25/793 vs. 46/4523, P = 2.56e-5). Replication in an independent cohort provided more supporting evidence. Further comparisons revealed that ALPK3 carriers displayed more severe hypertrophy in interventricular septum (IVS) and apex, as well as greater maximal left ventricular wall thickness, relative to sarcomere negatives. ConclusionHeterozygous rare variants in ALPK3, both missense and truncating variants, are associated with HCM in East Asians.

引用

页数：8

共 20 条

[1] Genetic effects on gene expression across human tissues [J].

Aguet, Francois ;

Brown, Andrew A. ;

Castel, Stephane E. ;

Davis, Joe R. ;

He, Yuan ;

Jo, Brian ;

Mohammadi, Pejman ;

Park, Yoson ;

Parsana, Princy ;

Segre, Ayellet V. ;

Strober, Benjamin J. ;

Zappala, Zachary ;

Cummings, Beryl B. ;

Gelfand, Ellen T. ;

Hadley, Kane ;

Huang, Katherine H. ;

Lek, Monkol ;

Li, Xiao ;

Nedzel, Jared L. ;

Nguyen, Duyen Y. ;

Noble, Michael S. ;

Sullivan, Timothy J. ;

Tukiainen, Taru ;

MacArthur, Daniel G. ;

Getz, Gad ;

Management, Nih Program ;

Addington, Anjene ;

Guan, Ping ;

Koester, Susan ;

Little, A. Roger ;

Lockhart, Nicole C. ;

Moore, Helen M. ;

Rao, Abhi ;

Struewing, Jeffery P. ;

Volpi, Simona ;

Collection, Biospecimen ;

Brigham, Lori E. ;

Hasz, Richard ;

Hunter, Marcus ;

Johns, Christopher ;

Johnson, Mark ;

Kopen, Gene ;

Leinweber, William F. ;

Lonsdale, John T. ;

McDonald, Alisa ;

Mestichelli, Bernadette ;

Myer, Kevin ;

Roe, Bryan ;

Salvatore, Michael ;

Shad, Saboor .

NATURE, 2017, 550 (7675) :204-+

[2] Phenotypic spectrum of ALPK3-related cardiomyopathy [J].

Al Senaidi, Khalfan ;

Joshi, Niranjan ;

Al-Nabhani, Maryam ;

Al-Kasbi, Ghalia ;

Al Farqani, Abdullah ;

Al-Thihli, Khalid ;

Al-Maawali, Almundher .

AMERICAN JOURNAL OF MEDICAL GENETICS PART A, 2019, 179 (07) :1235-1240

[3] Biallelic Truncating Mutations in ALPK3 Cause Severe Pediatric Cardiomyopathy [J].

Almomani, Rowida ;

Verhagen, Judith M. A. ;

Herkert, Johanna C. ;

Brosens, Erwin ;

van Spaendonck-Zwarts, Karin Y. ;

Asimaki, Angeliki ;

van der Zwaag, Paul A. ;

Frohn-Mulder, Ingrid M. E. ;

Bertoli-Avella, Aida M. ;

Boven, Ludolf G. ;

van Slegtenhorst, Marjon A. ;

van der Smagt, Jasper J. ;

van IJcken, Wilfred F. J. ;

Timmer, Bert ;

van Stuijvenberg, Margriet ;

Verdijk, Rob M. ;

Saffitz, Jeffrey E. ;

du Plessis, Frederik A. ;

Michels, Michelle ;

Hofstra, Robert M. W. ;

Sinke, Richard J. ;

van Tintelen, J. Peter ;

Wessels, Marja W. ;

Jongbloed, Jan D. H. ;

van de Laar, Ingrid M. B. H. .

JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY, 2016, 67 (05) :515-525

[4]

Caglayan AO, 2017, CSH MOL CASE STUD, V3, DOI 10.1101/mcs.a001859

[5] A Pathogenic Variant in ALPK3 Is Associated With an Autosomal Dominant Adult-onset Hypertrophic Cardiomyopathy [J].

Cheawsamoot, Chanatjit ;

Phokaew, Chureerat ;

Chetruengchai, Wanna ;

Chantranuwat, Poonchavist ;

Puwanant, Sarinya ;

Tongsima, Sissades ;

Khongphatthanayothin, Apichai ;

Shotelersuk, Vorasuk .

CIRCULATION-GENOMIC AND PRECISION MEDICINE, 2020, 13 (06) :722-724

[6] RBM20 Is a Candidate Gene for Hypertrophic Cardiomyopathy [J].

Dai, Jiaqi ;

Li, Zongzhe ;

Huang, Wei ;

Chen, Peng ;

Sun, Yang ;

Wang, Hong ;

Wu, Dongyang ;

Chen, Yanghui ;

Li, Chenze ;

Xiao, Lei ;

Liu, Hao ;

Wei, Haoran ;

Li, Rui ;

Duan, Quanlu ;

Peng, Liyuan ;

Song, Xiuli ;

Yu, Ting ;

Wang, Yan ;

Wang, Dao Wen .

CANADIAN JOURNAL OF CARDIOLOGY, 2021, 37 (11) :1751-1759

[7] Integrative approaches for large-scale transcriptome-wide association studies [J].

Gusev, Alexander ;

Ko, Arthur ;

Shi, Huwenbo ;

Bhatia, Gaurav ;

Chung, Wonil ;

Penninx, Brenda W. J. H. ;

Jansen, Rick ;

de Geus, Eco J. C. ;

Boomsma, Dorret I. ;

Wright, Fred A. ;

Sullivan, Patrick F. ;

Nikkola, Elina ;

Alvarez, Marcus ;

Civelek, Mete ;

Lusis, Aldons J. ;

Lehtimaki, Terho ;

Raitoharju, Emma ;

Kahonen, Mika ;

Seppala, Ilkka ;

Raitakari, Olli T. ;

Kuusisto, Johanna ;

Laakso, Markku ;

Price, Alkes L. ;

Pajukanta, Paivi ;

Pasaniuc, Bogdan .

NATURE GENETICS, 2016, 48 (03) :245-252

[8] Common genetic variants and modifiable risk factors underpin hypertrophic cardiomyopathy susceptibility and expressivity [J].

Harper, Andrew R. ;

Goel, Anuj ;

Grace, Christopher ;

Thomson, Kate L. ;

Petersen, Steffen E. ;

Xu, Xiao ;

Waring, Adam ;

Ormondroyd, Elizabeth ;

Kramer, Christopher M. ;

Ho, Carolyn Y. ;

Neubauer, Stefan ;

Tadros, Rafik ;

Ware, James S. ;

Bezzina, Connie R. ;

Farrall, Martin ;

Watkins, Hugh .

NATURE GENETICS, 2021, 53 (02) :135-+

[9] Expanding the clinical and genetic spectrum of ALPK3 variants: Phenotypes identified in pediatric cardiomyopathy patients and adults with heterozygous variants [J].

Herkert, Johanna C. ;

Verhagen, Judith M. A. ;

Yotti, Raquel ;

Haghighi, Alireza ;

Phelan, Dean G. ;

James, Paul A. ;

Brown, Natasha J. ;

Stutterd, Chloe ;

Macciocca, Ivan ;

Leong, Kai'En ;

Bulthuis, Marian L. C. ;

van Bever, Yolande ;

van Slegtenhorst, Marjon A. ;

Boven, Ludolf G. ;

Roberts, Amy E. ;

Agarwal, Radhika ;

Seidman, Jonathan ;

Lakdawala, Neal K. ;

Fernandez-Aviles, Francisco ;

Burke, Michael A. ;

Pierpont, Mary Ella ;

Braunlin, Elizabeth ;

Caglayan, Ahmet Okay ;

Barge-Schaapveld, Daniela Q. C. M. ;

Birnie, Erwin ;

Van Osch-Gevers, Lennie ;

van Langen, Irene M. ;

Jongbloed, Jan D. H. ;

Lockhart, Paul J. ;

Amor, David J. ;

Seidman, Christine E. ;

van de Laar, Ingrid M. B. H. .

AMERICAN HEART JOURNAL, 2020, 225 :108-119

[10] Novel ALPK3 mutation in a Tunisian patient with pediatric cardiomyopathy and facio-thoraco-skeletal features [J].

Jaouadi, Hager ;

Kraoua, Lilia ;

Chaker, Lilia ;

Atkinson, Alexandre ;

Delague, Valerie ;

Levy, Nicolas ;

Benkhalifa, Rym ;

Mrad, Ridha ;

Abdelhak, Sonia ;

Zaffran, Stephane .

JOURNAL OF HUMAN GENETICS, 2018, 63 (10) :1077-1082

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