Effect of hepatic lipase -514C->T polymorphism and its interactions with apolipoprotein C3 -482C->T and apolipoprotein E exon 4 polymorphisms on the risk of nephropathy in chinese type 2 diabetic patients.
OBJECTIVE
Triglyceride-rich lipoprotein particles may promote the progression of diabetic nephropathy. Patients with diabetic nephropathy have increased plasma triglycerides and reduced activity of hepatic lipase (HL), which hydrolyzes triglycerides. We hypothesized that the HL -514C-->T polymorphism, which reduces HL expression, and its interactions with polymorphisms in apolipoprotein (apo) E and apoC3 increase the risk of diabetic nephropathy.


METHODS
In a case-control study involving 374 Chinese type 2 diabetic patients with and 392 without diabetic nephropathy, we genotyped the HL -514C-->T, apoE exon 4, and apoC3 -482C-->T polymorphisms.


RESULTS
HL -514T-containing genotypes (T+) were associated with diabetic nephropathy (OR = 1.7, P = 0.0009). Adjustment by multiple logistic regression for hypertension, triglycerides, sex, non-HDL cholesterol, BMI, smoking, and alcohol intake did not diminish the association (OR = 1.8, P = 0.003). The association between HL T+ genotypes and diabetic nephropathy appeared stronger in diabetic patients with apoC3 -482 non-TT genotypes (OR = 1.9, P = 0.003) or apoE epsilon2 or epsilon4 alleles (OR = 2.2, P = 0.005). Subjects with HL TT exhibited trends toward increased triglyceride and non-HDL cholesterol levels compared with CC carriers.


CONCLUSIONS
HL T+ genotypes might increase the risk of developing diabetic nephropathy by slowing clearance of triglyceride-rich remnant lipoproteins. In concert with other risk factors (e.g., hyperglycemia), lipid abnormalities may damage the kidneys and endothelium, where reduced binding sites for lipases may precipitate a vicious cycle of dyslipidemia, proteinuria, and nephropathy.
Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong.
Larry
L
Baum
Maggie C Y
MC
Ng
Wing-Yee
WY
So
Vincent K L
VK
Lam
Ying
Y
Wang
Emily
E
Poon
Brian
B
Tomlinson
Suzanne
S
Cheng
Klaus
K
Lindpaintner
Juliana C N
JC
Chan
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C / Q000235:genetics*; D016022:Case-Control Studies; D002680:Chin; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000453:epidemiology* / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking; D014652:Vascular Diseases / Q000453:epidemiology / Q000235:genetics
D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; C504173:LIPC protein, human; D008049:Lipase