Apolipoprotein C-III protein concentrations and gene polymorphisms in Type 1 diabetes: associations with microvascular disease complications in the DCCT/EDIC cohort.
OBJECTIVE
We investigated the associations of apolipoprotein C-III (apoCIII) protein and apoCIII gene variation with microvascular disease complications in Type 1 diabetes.


METHODS
The serum apoCIII concentration, and both a T(-455)-->C and a SacI gene polymorphisms were determined in 409 patients in the DCCT/EDIC cohort of patients with Type 1 diabetes. Correlations with albumin excretion rate (AER) and the severity of retinopathy were investigated.


RESULTS
Higher apoCIII concentrations were associated (P<.0001) with increased triglycerides (r=.78), total (r=.61) and LDL (r=.40) cholesterol, apoAI (r=.26), and apoB (r=.50), AER (r=.08), and the severity of retinopathy (ETDRS score, r=.11), and these relationships persisted after controlling for age, gender, body mass index (BMI), and HbA1c level. The apoCIII concentration was significantly higher in the group of patients with macroalbuminuria (AERs 300 mg/24 h) compared to the groups with microalbuminuria (AER 40-299 mg/24 h; P<.0001) or normoalbuminuria (AER <40 mg/24 h) (P<.0001). The apoCIII concentration also was significantly higher in the group of patients with severe retinopathy (ETDRS 10-23) compared to those with moderate (ETDRS 4-9; P<.02) or mild retinopathy (ETDRS 1-3; P<.0001). Neither the T(-455)-->C polymorphism nor a SacI polymorphism in the 3' UTR were associated with circulating apoCIII concentrations, nor the severity of nephropathy or retinopathy.


CONCLUSIONS
Elevated apoCIII levels have been associated with increased macrovascular disease risk. In the DCCT/EDIC cohort of patients, there was an independent positive association of apoCIII level with microvascular complications of Type 1 diabetes.
Klein
Richard L
RL
Department of Medicine, Division of Endocrinology, Metabolism, and Medical Genetics, Medical University of South Carolina, Charleston, SC 29425, USA. kleinrl@musc.edu
McHenry
M Brent
MB
Lok
Kerry H
KH
Hunter
Steven J
SJ
Le
Ngoc-Anh
NA
Jenkins
Alicia J
AJ
Zheng
Deyi
D
Semler
Andrea
A
Page
Grier
G
Brown
W Virgil
WV
Lyons
Timothy J
TJ
Garvey
W Timothy
WT
D000328:Adult; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000097:blood* / Q000235:genetics*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003925:Diabetic Angiopathies / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D003930:Diabetic Retinopathy / Q000097:blood / Q000453:epidemiology / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology; D005838:Genotype; D006801:Humans; D008297:Male; D008833:Microcirculation; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012709:Serum Albumin / Q000378:metabolism; D012720:Severity of Illness Index
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D012709:Serum Albumin