Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians

TY - JOUR

T1 - Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians

AU - Cheema, Balneek Singh

AU - Iyengar, Sreenivasa

AU - Ahluwalia, Tarun Veer Singh

AU - Kohli, Harbir Singh

AU - Sharma, Rajni

AU - Shah, Viral N

AU - Bhansali, Anil

AU - Sakhuja, V

AU - Khullar, Madhu

N1 - Copyright © 2012 Elsevier B.V. All rights reserved.

PY - 2012/10/9

Y1 - 2012/10/9

N2 - Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients belonging to two independently ascertained cohorts using Real time PCR based Taqman assay. We observed a nearly threefold elevated risk of diabetic nephropathy among carriers of T allele and TT genotype of OPN C-443T polymorphism. Further, this allele was found to be significantly associated with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients.

AB - Genetic predisposition has been proposed to be a major determinant in the development of renal complications of diabetes. Osteopontin (OPN) has been suggested to be associated with renal diseases characterized by tubulointerstitial fibrosis and proteinuria. However, information on association of genetic polymorphisms in OPN with diabetic nephropathy is lacking. Thus, the present study was designed with the aim to examine the association of an OPN gene promoter polymorphism with diabetic nephropathy in Asian Indians. OPN C-443T (rs11730582) polymorphism was determined in 1115 type 2 diabetic patients belonging to two independently ascertained cohorts using Real time PCR based Taqman assay. We observed a nearly threefold elevated risk of diabetic nephropathy among carriers of T allele and TT genotype of OPN C-443T polymorphism. Further, this allele was found to be significantly associated with proteinuria and lower eGFR, a hallmark of diabetic nephropathy, in both our cohorts. This is the first study which suggests that OPN C-443T polymorphism may be a significant risk factor for diabetic nephropathy in type 2 diabetic patients.

KW - Aged

KW - Alleles

KW - Asian Continental Ancestry Group

KW - Diabetes Mellitus, Type 2

KW - Diabetic Nephropathies

KW - Female

KW - Gene Frequency

KW - Genetic Predisposition to Disease

KW - Glomerular Filtration Rate

KW - Humans

KW - India

KW - Kidney

KW - Male

KW - Middle Aged

KW - Osteopontin

KW - Polymorphism, Single Nucleotide

KW - Promoter Regions, Genetic

KW - Proteinuria

KW - Risk Factors

U2 - 10.1016/j.cca.2012.04.028

DO - 10.1016/j.cca.2012.04.028

M3 - Journal article

C2 - 22584029

SN - 1873-3492

VL - 413

SP - 1600

EP - 1604

JO - Clinica chimica acta; international journal of clinical chemistry

JF - Clinica chimica acta; international journal of clinical chemistry

IS - 19-20

ER -