Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese

Ronald Ching Wan Ma; Heung Man Lee; Vincent Kwok Lim Lam; Claudia Ha Ting Tam; Janice Siu Ka Ho; Hai Lu Zhao; Jing Guan; Alice Pik Shan Kong; Eric Lau; Guozhi Zhang; Andrea Luk; Ying Wang; Stephen Kwok Wing Tsui; Ting Fung Chan; Cheng Hu; Wei Ping Jia; Kyong Soo Park; Hong Kyu Lee; Hiroto Furuta; Kishio Nanjo; E. Shyong Tai; Daniel Peng Keat Ng; Nelson Leung Sang Tang; Jean Woo; Ping Chung Leung; Hong Xue; Jeffrey Wong; Po Sing Leung; Terrence C.K. Lau; Peter Chun Yip Tong; Gang XU; Maggie Chor Yin Ng; Wing Yee So; Juliana Chung Ngor Chan

doi:10.1371/journal.pone.0084770

Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese

Ronald Ching Wan Ma, Heung Man Lee, Vincent Kwok Lim Lam, Claudia Ha Ting Tam, Janice Siu Ka Ho, Hai Lu Zhao, Jing Guan, Alice Pik Shan Kong, Eric Lau, Guozhi Zhang, Andrea Luk, Ying Wang, Stephen Kwok Wing Tsui, Ting Fung Chan, Cheng Hu, Wei Ping Jia, Kyong Soo Park, Hong Kyu Lee, Hiroto Furuta, Kishio NanjoE. Shyong Tai, Daniel Peng Keat Ng, Nelson Leung Sang Tang, Jean Woo, Ping Chung Leung, Hong Xue, Jeffrey Wong, Po Sing Leung, Terrence C.K. Lau, Peter Chun Yip Tong, Gang XU, Maggie Chor Yin Ng, Wing Yee So, Juliana Chung Ngor Chan

School of Chinese Medicine

Research output: Contribution to journal › Journal article › peer-review

16 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e84770
Journal	PLoS ONE
Volume	9
Issue number	1
DOIs	https://doi.org/10.1371/journal.pone.0084770
Publication status	Published - 20 Jan 2014

Scopus Subject Areas

Biochemistry, Genetics and Molecular Biology(all)
Agricultural and Biological Sciences(all)
General

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10.1371/journal.pone.0084770

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Ma, R. C. W., Lee, H. M., Lam, V. K. L., Tam, C. H. T., Ho, J. S. K., Zhao, H. L., Guan, J., Kong, A. P. S., Lau, E., Zhang, G., Luk, A., Wang, Y., Tsui, S. K. W., Chan, T. F., Hu, C., Jia, W. P., Park, K. S., Lee, H. K., Furuta, H., ... Chan, J. C. N. (2014). Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese. PLoS ONE, 9(1), [e84770]. https://doi.org/10.1371/journal.pone.0084770

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title = "Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese",

abstract = "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.",

author = "Ma, {Ronald Ching Wan} and Lee, {Heung Man} and Lam, {Vincent Kwok Lim} and Tam, {Claudia Ha Ting} and Ho, {Janice Siu Ka} and Zhao, {Hai Lu} and Jing Guan and Kong, {Alice Pik Shan} and Eric Lau and Guozhi Zhang and Andrea Luk and Ying Wang and Tsui, {Stephen Kwok Wing} and Chan, {Ting Fung} and Cheng Hu and Jia, {Wei Ping} and Park, {Kyong Soo} and Lee, {Hong Kyu} and Hiroto Furuta and Kishio Nanjo and {Shyong Tai}, E. and Ng, {Daniel Peng Keat} and Tang, {Nelson Leung Sang} and Jean Woo and Leung, {Ping Chung} and Hong Xue and Jeffrey Wong and Leung, {Po Sing} and Lau, {Terrence C.K.} and Tong, {Peter Chun Yip} and Gang XU and Ng, {Maggie Chor Yin} and So, {Wing Yee} and Chan, {Juliana Chung Ngor}",

year = "2014",

month = jan,

day = "20",

doi = "10.1371/journal.pone.0084770",

language = "English",

volume = "9",

journal = "PLoS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

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Ma, RCW, Lee, HM, Lam, VKL, Tam, CHT, Ho, JSK, Zhao, HL, Guan, J, Kong, APS, Lau, E, Zhang, G, Luk, A, Wang, Y, Tsui, SKW, Chan, TF, Hu, C, Jia, WP, Park, KS, Lee, HK, Furuta, H, Nanjo, K, Shyong Tai, E, Ng, DPK, Tang, NLS, Woo, J, Leung, PC, Xue, H, Wong, J, Leung, PS, Lau, TCK, Tong, PCY, XU, G, Ng, MCY, So, WY & Chan, JCN 2014, 'Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese', PLoS ONE, vol. 9, no. 1, e84770. https://doi.org/10.1371/journal.pone.0084770

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

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.

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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 -

Familial young-onset diabetes, pre-diabetes and cardiovascular disease are associated with genetic variants of DACH1 in Chinese

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