Abstract
The objective of this paper is to investigate co-inheritance of specific HSPG and ApoE genotypes in the development of Chinese type 2 diabetic nephropathy. PCR-RFLP was used to detect HSPG and ApoE genotypes in 385 Chinese subjects including 298 patients with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls (Non-DM). The T2DM group was subdivided into patients with (TDN; n = 218) and without diabetic nephropathy (Non-DN; n = 80). The latter group was further subdivided into groups of patients with microalbuminuria nephropathy (DN-1; n = 129) and severe diabetic nephropathy (DN-2; n = 89). We then compared the relative frequencies of various HSPG and ApoE genotypes and alleles among the groups, searching for predictive trends. The T allele of the HSPG gene occurred more frequently in the DN-2 group than in the Non-DN or DN-1 or groups, their (Fisher's exact p was 1.05 × 10−3 and 6.58 × 10−6; odds ratios were 2.09 (95% CI 1.32–3.30) and 2.48 (95% CI 1.64–3.74), respectively. The E2 allele of the ApoE gene occurred more frequently in the T2DM than in the Non-DM group, the Fisher's exact p was 0.0087; odds ratio was 3.45 (95% CI 1.30–9.81). Genotype analysis showed that the TT or TG of HSPG gene were paired with the E2/2 or E2/3 of ApoE gene significantly more frequently in the TDN group than in the Non-DN group, with an odds ratio of 3.03 (95% CI 1.03–8.90). There was no significant differences in other combinations of genotypes in HSPG and ApoE genes between TDN and Non-DN group. These results suggest that the HSPG T allele is a risk factor for the development of severe diabetic nephropathy in type 2 diabetic patients, and that the ApoE E2 allele is a risk factor for the occurrence of type 2 diabetes mellitus in Chinese general population. In addition, we find that co-inheritance of T/E2 confers a higher risk of type 2 diabetes mellitus progression to diabetic nephropathy in Chinese.
Similar content being viewed by others
References
Chowdhury TA, Dyer PH, Kumar S et al.: Genetic determinants of diabetic nephropathy. Clin Sci 96: 221-230, 1999
Hansen PM, Chowdhury T, Deckert T, Hellgren A, Bain SC, Pociot F: Genetic variation of the heparin sulfate proteoglycan gene (perlecan gene), association with urinary albumin excretion in IDDM patients. Diabetes 46: 1658-1659, 1997
Eto M, Saito M, Okada M, Kume Y, Kawasaki F, Matsuda M, Yoneda M, Matsuki M, Takigami S, Kaku K: Apolipoprotein E genetic polymorphism, remnant lipoproteins, and nephropathy in type 2 diabetic patients. Am J Kidney Dis 40: 243-251, 2002
Lindahl U, Kusche M, Lidholt K, Oscarsson L-G: Biosynthesis of heparin and heparan sulfate. In: Heparin and Related Polysaccharides: Structure and Activities. Ann NY Acad Sci 556: 36-50, 1989
Tamsma J-T, van den Born J, Bruijn JA, Assmann KJM, Weening JJ: Expression of glomerular extracellular matrix components in human diabetic nephropathy: Decrease of heparin sulfate in the glomerular basement membrane. Diabetologia 37: 313-320, 1994
Blue ML, Williams DL, Zucker S, Khan SA, Blum CB. Apolipoprotein E synthesis in human kidney, adrenal gland and liver. Proc Natl Acad Sci USA 80: 283-287, 1983
Mahley RW, Innerarity TL: Lipoprotein receptors and cholesterol homeostasis. Biochem Biophys Acta 737: 197-222, 1983
Moorhead JF, Chan MK, El-Nahas M, Varghese Z: Lipid nephrotoxicity in chronic progressive glomerular and tubulointerstitial disease. Lancet 2: 1309-1311, 1982
Richard P, Thomas G, Zulueta MP et al.: Common and rare genotypes of human apolipoprotein E determined by specific restriction profiles of polymerase chain reaction-amplified DNA. Clin Chem 40: 24, 1994
Ukkola O, Kervinen K, Salmela PI et al.: Apolipoprotein E phenotype is related to macro and microangiopathy in patients with non-insulin-dependent diabetes mellitus. Atherosclerosis 101: 9-15, 1993
Tahseen AC, Philip HD, Sudesk K et al.: Association of apolipoprotein E2 allele with diabetic nephropathy in caucasian subjects with IDDM. Diabetes 47: 278, 1998
Pettitt DJ, Saad MF, Bennett PH, Nelson RG, Knowler WC: Familial predisposition to renal disease in two generations of Pima Indians with type 2 (non-insulin-dependent diabetes mellitus). Diabetologia 33: 438-443, 1990
Freedman BI, Tuffle AB, Spray BJ: Familial predisposition to nephropathy in African American with non-insulin-dependent diabetes mellitus. Am J Kidney Dis 25: 710-713, 1995
Scherbak NS: Apolipoprotein E gene polymorphism is not a strong risk factor for diabetic nephropathy and retinopathy in type I diabetes: Case-control study. BMC Med Genet 2: 8, 2001
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Liu, L., Xiang, K., Zheng, T. et al. Co-inheritance of specific genotypes of HSPG and ApoE gene increases risk of type 2 diabetic nephropathy. Mol Cell Biochem 254, 353–358 (2003). https://doi.org/10.1023/A:1027364121738
Issue Date:
DOI: https://doi.org/10.1023/A:1027364121738