Dr. Tarunveer Singh Ahluwalia

Hjelt grant holder 2009, Lund university

Identification of genetic susceptibility loci associated with diabetic nephropathy (DN) in Europeans

Dr. Tarunveer Singh Ahluwalia, PhD, received the postdoctoral fellowship from the Bo and Kerstin Hjelt Foundation for two years (March 2009 to February 2011). He holds a Master’s degree in Biotechnology from Panjab University, Chandigarh, India and was awarded his PhD degree at the Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India on his work titled “Functional Genomic Approaches to study the influence of genetic factors on the development of diabetic nephropathy”.

He started his Hjelt Foundation-funded project under the guidance of Prof. Leif Groop at the prestigious Lund University Diabetes Centre, Malmo, Sweden, focusing on identification of genetic susceptibility loci associated with diabetic nephropathy (DN) in Europeans.

DN is one of the most severe complications of type 1 and type 2 diabetes mellitus, and the leading cause of end-stage renal disease (ESRD) and renal replacement therapy. DN results from a complex interaction between genetic susceptibility and the diabetic environment characterised by poor glycaemic control and hypertension. About 35% of type 2 diabetic patients develop diabetic nephropathy. Familial clustering has been reported supporting the presence of a genetic component.

Based on these facts Dr. Ahluwalia initiated some projects: a) Carnosinase Dipeptidase (CNDP1 and CNDP2) variants and risk of DN: Among one of the loci identified in linkage scans chromosome 18q harboring CNDP1 and CNDP2 genes is a locus associating with DN. The former encodes a dipeptidase that hydrolyses the substrate L-carnosine (β-alanyl-L-histidine) specifically, while CNDP2 encodes a non-specific dipeptidase. Carnosine has been ascribed a protective role in diabetic nephropathy, since it serves as a scavenger of oxygen radicals and thus can inhibit formation of AGEs. Against this background, Dr. Ahluwalia tested whether there is an association between genetic variants (single nucleotide polymorphisms, SNPs) in the CNDP locus and DN in a large population of patients with type 2 diabetes from southern Sweden (Scania Diabetes Registry). He identified two SNPs (rs7577 in CNDP2 and rs2346061 in CNDP1) in the regulatory regions associating with risk of DN where rs7577 was also associated with an altered kidney function particularly in women [1].

b) Uromodulin gene (UMOD) variant and DN: Dr. Ahluwalia also tested the association of a genetic variant (rs13333226) in the UMOD gene which encodes the most common protein in human urine and risk of DN. This variant was previously identified to be associated with hypertension and chronic kidney disease in a genome wide association setting but had never been tested for association with DN. He found this variant to be associated with DN among the Swedish population [2].

c) He was involved in a couple of other projects where he contributed as a co-author. His first contribution involved in writing a review on the genetics of type 2 diabetes published in the year 2011 [3]. d) Another project where he was a co-author and contributed in data research and analysis was focussed on evaluating the effects of common genetic variants associated with type 2 diabetes and glycemic traits on alpha and beta-cell function and insulin action in humans. [4].In addition to these Dr. Ahluwalia has also contributed to another project still under finalization with the ENGAGE consortia.

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