TY - JOUR
T1 - Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese
AU - Ma, Ronald Ching Wan
AU - Lee, Heung Man
AU - Lam, Vincent Kwok Lim
AU - Tam, Claudia Ha Ting
AU - Ho, Janice Siu Ka
AU - Zhao, Hai Lu
AU - Guan, Jing
AU - Kong, Alice Pik Shan
AU - Lau, Eric
AU - Zhang, Guozhi
AU - Luk, Andrea
AU - Wang, Ying
AU - Tsui, Stephen Kwok Wing
AU - Chan, Ting Fung
AU - Hu, Cheng
AU - Jia, Wei Ping
AU - Park, Kyong Soo
AU - Lee, Hong Kyu
AU - Furuta, Hiroto
AU - Nanjo, Kishio
AU - Shyong Tai, E.
AU - Ng, Daniel Peng Keat
AU - Tang, Nelson Leung Sang
AU - Woo, Jean
AU - Leung, Ping Chung
AU - Xue, Hong
AU - Wong, Jeffrey
AU - Leung, Po Sing
AU - Lau, Terrence C.K.
AU - Tong, Peter Chun Yip
AU - Xu, Gang
AU - Ng, Maggie Chor Yin
AU - So, Wing Yee
AU - Chan, Juliana Chung Ngor
N1 - This study was partly supported by the Research Grant Council (RGC) Central Allocation Scheme (CUHK 1/04C), RGC earmarked grant (CUHK4462/06M), US National Institutes of Health (U01-DK085545-05) as well as the Hong Kong Foundation for Research and Development in Diabetes and Liao Wun Yuk Diabetes Research Memorial Fund established under the CUHK. The research in Shanghai Chinese was supported by grants from National Natural Scientific Foundation of China (30630061) and Shanghai Key Laboratory of Diabetes Mellitus (08DZ2230200). The study in Korea was funded by a grant from the Korea Health 21 R&D Project, Ministry of Health, Welfare and Family Affair, Republic of Korea (00-PJ3-PG6-GN07-001 to K.S.P.). The work in Japan was supported by Grant-in-Aid for Scientific Research on Priority Areas ‘Applied Genomics’ no. 17019047 from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The Singapore Prospective Study Program was funded through grants from the Biomedical Research Council of Singapore (BMRC 05/1/36/19/413 and 03/1/27/18/216) and the National Medical Research Council of Singapore (NMRC/1174/2008). The Singapore Malay Eye Study was funded by the National Medical Research Council (NMRC 0796/2003, IRG07nov013, and NMRC/STaR/0003/2008) and Biomedical Research Council (BMRC, 09/1/35/19/616). EST also receives additional support from the National Medical Research Council through a clinician scientist award.
PY - 2014/1/20
Y1 - 2014/1/20
N2 - In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57-3.96, P = 8.4 × 10-5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02-1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214) and 3.27(1.25-11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese.
AB - In Asia, young-onset type 2 diabetes (YOD) is characterized by obesity and increased risk for cardiovascular disease (CVD). In a genome-wide association study (GWAS) of 99 Chinese obese subjects with familial YOD diagnosed before 40-year-old and 101 controls, the T allele of rs1408888 in intron 1 of DACH1(Dachshund homolog 1) was associated with an odds ratio (OR) of 2.49(95% confidence intervals:1.57-3.96, P = 8.4 × 10-5). Amongst these subjects, we found reduced expression of DACH1 in peripheral blood mononuclear cells (PBMC) from 63 cases compared to 65 controls (P = 0.02). In a random cohort of 1468 cases and 1485 controls, amongst top 19 SNPs from GWAS, rs1408888 was associated with type 2 diabetes with a global P value of 0.0176 and confirmation in a multiethnic Asian case-control cohort (7370/7802) with an OR of 1.07(1.02-1.12, Pmeta = 0.012). In 599 Chinese non-diabetic subjects, rs1408888 was linearly associated with systolic blood pressure and insulin resistance. In a case-control cohort (n = 953/953), rs1408888 was associated with an OR of 1.54(1.07-2.22, P = 0.019) for CVD in type 2 diabetes. In an autopsy series of 173 non-diabetic cases, TT genotype of rs1408888 was associated with an OR of 3.31(1.19-9.19, P = 0.0214) and 3.27(1.25-11.07, P = 0.0184) for coronary heart disease (CHD) and coronary arteriosclerosis. Bioinformatics analysis revealed that rs1408888 lies within regulatory elements of DACH1 implicated in islet development and insulin secretion. The T allele of rs1408888 of DACH1 was associated with YOD, prediabetes and CVD in Chinese.
UR - http://www.scopus.com/inward/record.url?scp=84907973860&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0084770
DO - 10.1371/journal.pone.0084770
M3 - Journal article
C2 - 24465431
AN - SCOPUS:84907973860
SN - 1932-6203
VL - 9
JO - PLoS ONE
JF - PLoS ONE
IS - 1
M1 - e84770
ER -