Association of CTG repeat polymorphism in carnosine dipeptidase 1 (CNDP1) gene with diabetic nephropathy in north Indians.
OBJECTIVE
CNDP1 gene, present on chromosome 18q22.3-23, encodes carnosinase, the rate-limiting enzyme in hydrolysis of carnosine to ß-alanine and L-histidine. Linkage of CTG trinucleotide (leucine) repeat polymorphism in CNDP1 gene with diabetic nephropathy has been observed in several populations. However, this association is conflicting and population-dependent. We investigated this association in type 2 diabetes mellitus (T2DM) patients with and without nephropathy in north India.


METHODS
A total of 564 individuals [199 T2DM without nephropathy (DM), 185 T2DM with nephropathy (DN) and 180 healthy individuals (HC)] were enrolled. CNDP1 CTG repeat analysis was done by direct sequencing of a 377 base pair fragment in exon 2.


RESULTS
The most frequent leucine (L) repeats were 5L-5L, 6L-5L and 6L-6L. 5L-5L genotype frequency was reduced in DN (24.3%) as compared to DM (34.7%, P=0.035) and HC (38.4%, P=0.005). Similarly, 5L allele frequency was lower in DN (46.8%) as compared to DM (57.3%, P=0.004) and HC (60.5%, P<0.001). The genotype and allelic frequencies were similar in DM and HC groups. No gender specific difference was observed in the genotype or allelic frequencies between groups.


CONCLUSIONS
Compared to healthy individuals and those with diabetes but no kidney disease, patients with diabetic nephropathy exhibited lower frequencies of 5L-5L genotype and 5L allele of CNDP1 gene, suggesting that this allele might confer protection against development of kidney disease in this population.
Department of Nephrology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Ashok K
AK
Yadav
Department of Nephrology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Nisha
N
Sinha
Department of Nephrology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Vinod
V
Kumar
Department of Endocrinology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Anil
A
Bhansali
Department of Endocrinology, Post Graduate Institute of Medical Education & Research, Chandigarh, India.
Pinaki
P
Dutta
Department of Nephrology, Post Graduate Institute of Medical Education & Research, Chandigarh; George Institute for Global Health, New Delhi, India.
Vivekanand
V
Jha
D000293:Adolescent; D000328:Adult; D000368:Aged; D000483:Alleles; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics* / Q000473:pathology; D003928:Diabetic Nephropathies / Q000235:genetics* / Q000473:pathology; D004150:Dipeptidases / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018911:Trinucleotide Repeats / Q000235:genetics
C522928:CNDP1 protein, human; D004150:Dipeptidases