title: Association of an Osteopontin gene promoter polymorphism with susceptibility to diabetic nephropathy in Asian Indians.
abstract: 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.
authors.affiliation: Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medicine Education & Research, Chandigarh 160012, India.
authors.forename: Balneek Singh
authors.initials: BS
authors.lastname: Cheema
authors.forename: Sreenivasa
authors.initials: S
authors.lastname: Iyengar
authors.forename: Tarunveer Singh
authors.initials: TS
authors.lastname: Ahluwalia
authors.forename: Harbir Singh
authors.initials: HS
authors.lastname: Kohli
authors.forename: Rajni
authors.initials: R
authors.lastname: Sharma
authors.forename: Viral N
authors.initials: VN
authors.lastname: Shah
authors.forename: Anil
authors.initials: A
authors.lastname: Bhansali
authors.forename: V
authors.initials: V
authors.lastname: Sakhuja
authors.forename: Madhu
authors.initials: M
authors.lastname: Khullar
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000150:complications / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007194:India; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D053495:Osteopontin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D011507:Proteinuria / Q000150:complications / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: D053495:Osteopontin