Skip to main content

Advertisement

Log in

ApoA5-1131T→C polymorphism and its effect on triglyceride level in type 2 diabetes patients with nephropathy

  • Original Article
  • Published:
Comparative Clinical Pathology Aims and scope Submit manuscript

Abstract

Diabetic nephropathy (DN) is a major cause of end-stage renal disease. Epidemiological studies suggest genetic predisposition to DN. Apolipoprotein A5 (ApoA5) plays an important role in the triglyceride (TG) metabolism, accelerating the catabolism of the TG-rich lipoproteins. Studies revealed that the ApoA5-1131 polymorphism is strongly associated with TG levels affecting DN risk. Patients with DN have increased fasting plasma TG levels, and studies report that elevated TG precedes DN. To test the effect of polymorphism ApoA5-1131T→C on the elevated TG levels contributing to the development of DN on type 2 diabetes patients, the study was conducted on 40 diabetic patients divided into two groups according to the presence or absence of diabetic nephropathy (DN+ and DN−), compared to 20 age- and sex-matched apparently healthy controls. DNA analysis was performed using polymerase chain reaction–restriction fragment length polymorphism. ApoA5-1131 CC carriers had a higher mean TG in the DN+, DN−, and control groups (TG 224, 201, and 204 mg/dl, respectively) (p = 0.001) compared to TT and TC carriers. Genotype distribution between controls and patients revealed CC carriers in the DN− and DN+ to be 55 and 45 %, respectively, compared to only 15 % in the control group (p = 0.001). Association between DN and the polymorphism (CC) that affects fasting TG is seen in this study (OR = 4.6, 95 % CI = 1.02–21, p = 0.001). ApoA5-1131 CC carriers are more susceptible to a higher fasting TG level and the development of DN.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Bakris GL (2011) Recognition, pathogenesis, and treatment of different stages of nephropathy in patients with type 2 diabetes mellitus. Mayo Clin Proc 86(5):444–456

    Article  CAS  PubMed  Google Scholar 

  • Baum L, Ng MC, So WY, Poon E, Wang Y, Lam VK, Tomlinson B, Chan JC (2007) A case-control study of apoA5-1131T→C polymorphism that examines the role of triglyceride levels in diabetic nephropathy. J Diabetes Complicat 21(3):158–163

    Article  PubMed  Google Scholar 

  • Bonnet F, Cooper ME (2000) Potential influence of lipids in diabetic nephropathy: insights from experimental data and clinical studies. Diabetes Metab 26:254–264

    CAS  PubMed  Google Scholar 

  • Colhoun HM, Lee ET, Bennett PH, Lu M, Keen H, Wang SL, Stevens LK, Fuller JH (2001) Risk factors for renal failure: the WHO multinational study of vascular disease in diabetes. Diabetologia 44(Suppl 2):S46–S53

    Article  CAS  PubMed  Google Scholar 

  • Coonrod BA, Ellis D, Becker DJ, Bunker CH, Kelsey SF, Lloyd CE, Drash AL, Kuller LH, Orchard TJ (1993) Predictors of microalbuminuria in individuals with IDDM. Pittsburgh epidemiology of diabetes complications study. Diabetes Care 16:1376–1383

    Article  CAS  PubMed  Google Scholar 

  • Dorfmeister B, Cooper JA, Stephens JW, Ireland H, Hurel SJ, Humphries SE, Talmud PJ (2006) The effect of APOA5 and APOC3 variants on lipid parameters in European Whites, Indian Asians and Afro-Caribbean’s with type 2 diabetes. Biochim Biophys Acta 1772(3):355–363

    Article  PubMed  Google Scholar 

  • Evans D, Buchwald A, Beil FU (2003) The single nucleotide polymorphism -1131T>C in the apolipoprotein A5 (APOA5) gene is associated with elevated triglycerides in patients with hyperlipidemia. J Mol Med 81:645–654

    Google Scholar 

  • Fagot-Campagna A, Nelson RG, Knowler WC, Pettitt DJ, Robbins DC, Go O, Welty TK, Lee ET, Howard BV (1998) Plasma lipoproteins and the incidence of abnormal excretion of albumin in diabetic American Indians: the strong heart study. Diabetologia 41:1002–1009

    Article  CAS  PubMed  Google Scholar 

  • Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18(6):499–502

    CAS  PubMed  Google Scholar 

  • Giorgino F, Laviola L, Cavallo PP, Solnica B, Fuller J, Chaturvedi N (2004) Factors associated with progression to macroalbuminuria in microalbuminuric type 1 diabetic patients: the EURODIAB prospective complications study. Diabetologia 47:1020–1028

    Article  CAS  PubMed  Google Scholar 

  • Hadjadj S, Duly-Bouhanick B, Bekherraz A, Brldoux F, Gallois Y, Mauco G, Ebran J, Marre M (2004) Serum triglycerides are a predictive factor for the development and the progression of renal and retinal complications in patients with type 1 diabetes. Diabetes Metab 30:43–51

    Article  CAS  PubMed  Google Scholar 

  • Hubacek JA, Skodová Z, Adámková V, Lánská V, Pitha J (2005) APOA5 variant Ser19Trp influences a decrease of the total cholesterol in a male 8 year cohort. Clin Biochem 39(2):133–136

    Article  PubMed  Google Scholar 

  • Iseki K, Ottawa M, Ikemiya Y, Kinjo K, Iseki C, Takishita S (2005) Relationship between dyslipidemia and the risk of developing end-stage renal disease in a screened cohort. Clin Exp Nephrol 9:46–52

    Article  PubMed  Google Scholar 

  • Jang Y, Kim JY, Kim OY, Lee JE, Cho H, Ordovas JM, Lee JH (2004) The -1131T- C polymorphism in the apolipoprotein A5 gene is associated with postprandial hypertriacylglycerolemia; elevated small, dense LDL concentrations; and oxidative stress in non obese Korean men. Am J Clin Nutr 80(4):832–840

    CAS  PubMed  Google Scholar 

  • Jenkins AJ, Lyons TJ, Zhen D, Octavos JD, Lockland DT, McGee D, Garvey WT, Klein RL (2003) Lipoproteins in the DCCT/EDIC cohort: associations with diabetic nephropathy. Kidney Int 64:817–828

    Article  CAS  PubMed  Google Scholar 

  • Kim DM, An CW, Park JS, Cha BS, Lim SK, Kim KR, Lee HC, Huh KB (2004) An implication of hypertriglyceridemia in the progression of diabetic nephropathy in metabolically obese, normal weight patients with type 2 diabetes mellitus in Korea. Diabetes Res Clin Pract 66(Suppl 1):S169–S172

    Article  CAS  PubMed  Google Scholar 

  • Knapp RG, Miller MC (1992) Describing the performance of a diagnostic test. Clinical epidemiology and biostatistics. Williams & Wilkins, Baltimore, p 42

    Google Scholar 

  • Lai CQ, Tai ES, Tan CE, Cutter J, Chew SK, Zhu YP, Adiconis X, Ordovas JM (2003) The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. J Lipid Res (12):2365–2373

  • Lai CQ, Tai ES, Tan CE et al (2004) The APOA5 locus is a strong determinant of plasma triglyceride concentrations across ethnic groups in Singapore. J Lipid Res 44(12):2365–2373

    Google Scholar 

  • Levey AS, Stevens LA, Schmid CH, Zhang Y, Castro AF III, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, for the CKD-EPI (2009) Chronic kidney disease epidemiology collaboration. A new equation. Ann Intern Med 150(9):604–612

    Article  PubMed Central  PubMed  Google Scholar 

  • Muntner P, Coresh J, Smith JC, Eckfeldt J, Klag MJ (2000) Plasma lipids and risk of developing renal dysfunction: the atherosclerosis risk in communities study. Kidney Int 58:293–301

    Article  CAS  PubMed  Google Scholar 

  • Orchard TJ, Forrest KY, Kuller LH, Becker DJ (2001) Lipid and blood pressure treatment goals for type 1 diabetes: 10-yearincidence data from the Pittsburgh epidemiology of diabetes complications study. Diabetes Care 24:1053–1059

    Article  CAS  PubMed  Google Scholar 

  • Pennacchio LA, Olivier M, Hubacek JA, Cohen JC, Cox DR, Fruchart JC, Krauss RM, Rubin EM (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173

    Article  CAS  PubMed  Google Scholar 

  • Ravid M, Brosh D, Ravid-Safran D, Levy Z, Rachmani R (1998) Main risk factors for nephropathy in type 2 diabetes mellitus are plasma cholesterol levels, mean blood pressure, and hyperglycemia. Arch Intern Med 158:998–1004

    Article  CAS  PubMed  Google Scholar 

  • Sousa MO, Corbella E, Alía P, Cámara J, Castro MJ, Pintó X, Navarro MA (2008) Lack of association between the APOE genotype and the response to Statin treatment in patients with acute ischemic episodes. Med Clini (Barc) 29(130(11)):401–404

    Article  Google Scholar 

  • Talmud PJ, Hawe E, Miller GJ, Humphries SE (2003) Nonfasting apolipoprotein B and triglyceride levels as a useful predictor of coronary heart disease risk in middle-aged UK men. Arterioscler Thromb Vasc Biol 1;22(11):1918–1923

    Google Scholar 

  • Talmud PJ, Martin S, Taskinen MR, Frick MH, Nieminen MS, Kesäniemi YA, Pasternack A, Humphries SE, Syvänne M (2004) ApoA5 gene variants, lipoprotein particle distribution, and progression of coronary heart disease: results from the LOCAT study. J Lipid Res 45(4):750–756

    Article  CAS  PubMed  Google Scholar 

  • van deer Vliet HN, Schaap FG, Levels JH, Ottenhoff R, Looije N, Wesseling JG, Groen AK, Chamuleau RA (2002) Adenoviral over expression of apolipoprotein A-V reduces serum levels of triglycerides and cholesterol in mice. Biochem Biophys Res Commun 295:1156–1159

    Article  PubMed  Google Scholar 

  • Wang Y, Ng MC, Lee SC, So WY, Tong PC, Cockram CS, Critchley JA, Chan JC (2003) Phenotypic heterogeneity and associations of two aldose reductase gene polymorphisms with nephropathy and retinopathy in type 2 diabetes. Diabetes Care 26:2410–2415

    Article  CAS  PubMed  Google Scholar 

  • World Health Organization (WHO) (2011) Diabetes. Fact sheet No. 312

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dina ELabd.

Rights and permissions

Reprints and permissions

About this article

Cite this article

ELabd, D., Fayad, T. ApoA5-1131T→C polymorphism and its effect on triglyceride level in type 2 diabetes patients with nephropathy. Comp Clin Pathol 23, 145–150 (2014). https://doi.org/10.1007/s00580-012-1586-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00580-012-1586-3

Keywords

Navigation