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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.
Diabetes Care. 2005 Jul; 28(7):1704-9.DC

Abstract

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.

RESEARCH DESIGN AND 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.

Authors+Show Affiliations

Department of Medicine and Therapeutics, Chinese University of Hong Kong, Shatin, Hong Kong.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

15983323

Citation

Baum, Larry, et al. "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." Diabetes Care, vol. 28, no. 7, 2005, pp. 1704-9.
Baum L, Ng MC, So WY, et al. 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. Diabetes Care. 2005;28(7):1704-9.
Baum, L., Ng, M. C., So, W. Y., Lam, V. K., Wang, Y., Poon, E., Tomlinson, B., Cheng, S., Lindpaintner, K., & Chan, J. C. (2005). 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. Diabetes Care, 28(7), 1704-9.
Baum L, et al. 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. Diabetes Care. 2005;28(7):1704-9. PubMed PMID: 15983323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Baum,Larry, AU - Ng,Maggie C Y, AU - So,Wing-Yee, AU - Lam,Vincent K L, AU - Wang,Ying, AU - Poon,Emily, AU - Tomlinson,Brian, AU - Cheng,Suzanne, AU - Lindpaintner,Klaus, AU - Chan,Juliana C N, PY - 2005/6/29/pubmed PY - 2005/9/24/medline PY - 2005/6/29/entrez SP - 1704 EP - 9 JF - Diabetes care JO - Diabetes Care VL - 28 IS - 7 N2 - 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. RESEARCH DESIGN AND 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. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/15983323/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_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=15983323 DB - PRIME DP - Unbound Medicine ER -