Identification of a Common Variant for Coronary Heart Disease at PDE1A Contributes to Individualized Treatment Goals and Risk Stratification of Cardiovascular Complications in Chinese Patients With Type 2 Diabetes

被引:7
|
作者
Tam, Claudia H. T. [1 ,2 ,3 ]
Lim, Cadmon K. P. [1 ,2 ,3 ]
Luk, Andrea O. Y. [1 ,2 ,3 ,4 ]
Shi, Mai [1 ,2 ,3 ]
Cheung, Hoi Man [1 ,2 ]
Ng, Alex C. W. [1 ]
Lee, Heung-man [1 ,2 ]
Lau, Eric S. H. [1 ]
Fan, Baoqi [1 ,2 ,3 ]
Jiang, Guozhi [5 ]
Kong, Alice P. S. [1 ,2 ,4 ]
Ozaki, Risa [1 ]
Chow, Elaine Y. K. [1 ,2 ]
Lee, Ka Fai [6 ]
Siu, Shing Chung [7 ]
Hui, Grace [7 ]
Tsang, Chiu Chi [8 ]
Lau, Kam Piu [9 ]
Leung, Jenny Y. Y. [10 ]
Cheung, Elaine Y. N. [11 ]
Tsang, Man Wo [11 ]
Kam, Grace [11 ]
Lau, Ip Tim [12 ]
Li, June K. Y. [13 ]
Yeung, Vincent T. F. [14 ]
Lau, Emmy [15 ]
Lo, Stanley [15 ]
Fung, Samuel [16 ]
Cheng, Yuk Lun [17 ]
Chow, Chun Chung [1 ]
Fan, Xiaodan [18 ]
Chan, Ting Fung [19 ]
Yip, Kevin Y. L. [20 ]
Lok, Si [21 ]
Yu, Weichuan [22 ]
Tsui, Stephen K. W. [23 ]
Lan, Hui-Yao [1 ,4 ]
Szeto, Cheuk Chun [1 ]
Tang, Nelson L. S. [4 ,24 ]
Tomlinson, Brian [25 ]
Huang, Yu [26 ]
Jenkins, Alicia J. [27 ]
Keech, Anthony [27 ]
So, Wing-Yee [1 ,2 ]
Chan, Juliana C. N. [1 ,2 ,3 ,4 ]
Ma, Ronald C. W. [1 ,2 ,3 ,4 ]
机构
[1] Chinese Univ Hong Kong, Dept Med & Therapeut, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Hong Kong Inst Diabet & Obes, Hong Kong, Peoples R China
[3] Chinese Univ Hong Kong, CUHK SJTU Joint Res Ctr Diabet Genom & Precis Med, Hong Kong, Peoples R China
[4] Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Peoples R China
[5] Sun Yat Sen Univ, Sch Publ Hlth Shenzhen, Shenzhen, Guangdong, Peoples R China
[6] Kwong Wah Hosp, Dept Med & Geriatr, Hong Kong, Peoples R China
[7] Tung Wah Eastern Hosp, Ctr Diabet, Hong Kong, Peoples R China
[8] Alice Ho Miu Ling Nethersole Hosp, Diabet & Educ Ctr, Hong Kong, Peoples R China
[9] North Dist Hosp, Hong Kong, Peoples R China
[10] Ruttonjee Hosp, Dept Med & Geriatr, Hong Kong, Peoples R China
[11] United Christian Hosp, Dept Med & Geriatr, Hong Kong, Peoples R China
[12] Tseung Kwan O Hosp, Hong Kong, Peoples R China
[13] Yan Chai Hosp, Dept Med, Hong Kong, Peoples R China
[14] Our Lady Maryknoll Hosp, Ctr Diabet Educ & Management, Hong Kong, Peoples R China
[15] Pamela Youde Nethersole Eastern Hosp, Dept Med, Hong Kong, Peoples R China
[16] Princess Margaret Hosp, Dept Med & Geriatr, Hong Kong, Peoples R China
[17] Alice Ho Miu Ling Nethersole Hosp, Dept Med, Hong Kong, Peoples R China
[18] Chinese Univ Hong Kong, Dept Stat, Hong Kong, Peoples R China
[19] Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Peoples R China
[20] Chinese Univ Hong Kong, Dept Comp Sci & Engn, Hong Kong, Peoples R China
[21] Hosp Sick Children, Ctr Appl Genom, Toronto, ON, Canada
[22] Hong Kong Univ Sci & Technol, Dept Elect & Comp Engn, Hong Kong, Peoples R China
[23] Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Peoples R China
[24] Chinese Univ Hong Kong, Dept Chem Pathol, Hong Kong, Peoples R China
[25] Macau Univ Sci & Technol, Fac Med, Cotai, Macau, Peoples R China
[26] City Univ Hong Kong, Dept Biomed Sci, Hong Kong, Peoples R China
[27] Univ Sydney, NHMRC Clin Trials Ctr, Sydney, NSW, Australia
关键词
SUSCEPTIBILITY LOCI; ASSOCIATION; MECHANISMS; MELLITUS; GLUCOSE;
D O I
10.2337/dc22-2331
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVEIn this study we aim to unravel genetic determinants of coronary heart disease (CHD) in type 2 diabetes (T2D) and explore their applications. RESEARCH DESIGN AND METHODSWe performed a two-stage genome-wide association study for CHD in Chinese patients with T2D (3,596 case and 8,898 control subjects), followed by replications in European patients with T2D (764 case and 4,276 control subjects) and general populations (n = 51,442-547,261). Each identified variant was examined for its association with a wide range of phenotypes and its interactions with glycemic, blood pressure (BP), and lipid controls in incident cardiovascular diseases. RESULTSWe identified a novel variant (rs10171703) for CHD (odds ratio 1.21 [95% CI 1.13-1.30]; P = 2.4 x 10(-8)) and BP (beta +/- SE 0.130 +/- 0.017; P = 4.1 x 10(-14)) at PDE1A in Chinese T2D patients but found only a modest association with CHD in general populations. This variant modulated the effects of BP goal attainment (130/80 mmHg) on CHD (P-interaction = 0.0155) and myocardial infarction (MI) (P-interaction = 5.1 x 10(-4)). Patients with CC genotype of rs10171703 had >40% reduction in either cardiovascular events in response to BP control (2.9 x 10(-8) < P < 3.6 x 10(-5)), those with CT genotype had no difference (0.0726 < P < 0.2614), and those with TT genotype had a threefold increase in MI risk (P = 6.7 x 10(-3)). CONCLUSIONSWe discovered a novel CHD- and BP-related variant at PDE1A that interacted with BP goal attainment with divergent effects on CHD risk in Chinese patients with T2D. Incorporating this information may facilitate individualized treatment strategies for precision care in diabetes, only when our findings are validated.
引用
收藏
页码:1271 / 1281
页数:12
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