Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese.
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, P(meta)  = 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.
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Ronald Ching Wan
RC
Ma
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Heung Man
HM
Lee
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Vincent Kwok Lim
VK
Lam
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Claudia Ha Ting
CH
Tam
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Janice Siu Ka
JS
Ho
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Hai-Lu
HL
Zhao
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Jing
J
Guan
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Alice Pik Shan
AP
Kong
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Eric
E
Lau
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Guozhi
G
Zhang
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Andrea
A
Luk
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Ying
Y
Wang
School of Biomedical Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Stephen Kwok Wing
SK
Tsui
School of Life Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Ting Fung
TF
Chan
Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Cheng
C
Hu
Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, People's Republic of China.
Wei Ping
WP
Jia
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and Department of Internal Medicine, College of Medicine, Seoul National University, Chongno-gu, Seoul, Korea.
Kyong Soo
KS
Park
Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology and Department of Internal Medicine, College of Medicine, Seoul National University, Chongno-gu, Seoul, Korea.
Hong Kyu
HK
Lee
First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
Hiroto
H
Furuta
First Department of Medicine, Wakayama Medical University, Wakayama, Japan.
Kishio
K
Nanjo
Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore.
E Shyong
ES
Tai
Department of Epidemiology and Public Health, National University of Singapore, Singapore, Singapore.
Daniel Peng-Keat
DP
Ng
Department of Chemical Pathology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Nelson Leung Sang
NL
Tang
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Jean
J
Woo
Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Ping Chung
PC
Leung
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong SAR, People's Republic of China.
Hong
H
Xue
Department of Biochemistry, Hong Kong University of Science and Technology, Hong Kong SAR, People's Republic of China.
Jeffrey
J
Wong
School of Biomedical Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Po Sing
PS
Leung
School of Biomedical Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Terrence C K
TC
Lau
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China.
Peter Chun Yip
PC
Tong
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Gang
G
Xu
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Maggie Chor Yin
MC
Ng
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Wing Yee
WY
So
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China ; Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong SAR, People's Republic of China ; Li Ka Shing Institute of Health Science, The Chinese University of Hong Kong, The Prince of Wales Hospital, Shatin, Hong Kong SAR, People's Republic of China.
Juliana Chung Ngor
JC
Chan
D000368:Aged; D044466:Asian People / Q000235:genetics; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005136:Eye Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011236:Prediabetic State / Q000453:epidemiology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*
C486747:DACH1 protein, human; D005136:Eye Proteins; D014157:Transcription Factors