Phenotypic and genetic clustering of diabetes and metabolic syndrome in Chinese families with type 2 diabetes mellitus.
BACKGROUND
The aim of this study was to investigate the familiality and clustering of type 2 diabetes (T2DM) and metabolic syndrome (MES) predominantly in families with young-onset diabetes from the Hong Kong Family Diabetes Study.


METHODS
One hundred and seventy-nine families (913 subjects) were ascertained through a diabetic proband. Anthropometry, glucose homeostasis, blood pressure and lipid levels were examined. Familial aggregation and inter-relationships of these traits were examined by recurrence risk ratio, heritability, genetic and environmental correlations.


RESULTS
One hundred and forty families (78%) had at least one subject with early-onset T2DM (age-at-diagnosis </=40 years). MES was highly prevalent in probands (53%) and siblings (25%). Recurrence risk ratios in siblings were high for T2DM (4.3), hypertension (2.9) and central obesity (2.0). Body mass index, waist circumference, blood pressure, plasma insulin, triglyceride, HDL-cholesterol levels, insulin resistance and beta-cell function had high estimates of heritability (0.45-0.63). Bivariate quantitative analyses revealed differential contribution of genetic and environmental factors to the phenotypic correlation between metabolic trait pairs. Obesity indices showed the strongest phenotypic correlation with other traits, and were significantly influenced by genetic factors (genetic correlation = 0.29-0.60).


CONCLUSIONS
There was significant familial aggregation of T2DM and related phenotypes including obesity, hypertension and dyslipidaemia. The clustering of metabolic traits is likely due to genetic effects, interacting with shared and unique lifestyle/environmental factors. The high familiality suggests that screening for MES is important, especially in families with young-onset diabetes, and that the families in HKFDS are valuable subjects for genetic studies of these metabolic diseases.
Li
J K Y
JK
Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong SAR, China.
Ng
M C Y
MC
So
W Y
WY
Chiu
C K P
CK
Ozaki
R
R
Tong
P C Y
PC
Cockram
C S
CS
Chan
J C N
JC
D000328:Adult; D002681:China / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D006946:Hyperinsulinism / Q000235:genetics / Q000378:metabolism; D006949:Hyperlipidemias / Q000235:genetics / Q000378:metabolism; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008659:Metabolic Diseases / Q000235:genetics / Q000378:metabolism; D024821:Metabolic Syndrome / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000378:metabolism*; D010641:Phenotype; D013577:Syndrome
D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007328:Insulin