Status of Single Nucleotide Polymorphism of Matrix Gla Protein Gene (rs4236) in Nephrolithiasis: A Preliminary Study in Indian Population

BACKGROUND: Urine is a supersaturated solution with solutes in very high concentration. Matrix gla protein (MGP) is one of the proteins involved in inhibition of extracellular calcification. Among the various polymorphisms studied, polymorphism of SNP rs4236 in the MGP gene is found to have association with nephrolithiasis. We evaluated the significance of SNP rs4236 polymorphism in nephrolithiasis among the Indian population. MATERIALS AND METHODS: The study was conducted in 2013 and 2014 among fifty participants. Twenty-five of them were patients with documented symptomatic stone disease and the 25 controls had no history of stone disease and ultrasonogram was normal. Serum creatinine was estimated in all patients. DNA was isolated from the blood sample and amplified by polymerase chain reaction using defined primers. Single strand conformational polymorphism was done to identify abnormal bands and the same was sequenced. RESULTS: The patients and controls were matched in age and sex. The serum creatinine levels were similar in both groups. The predominant change in SNP rs4236 in patients was a G to A nucleotide change, resulting in AA homozygous genotype. This was found in 60% of patients. The rest (40%) of patients and all (100%) controls had heterozygous AG genotype. This corresponds to a stone disease with an odds ratio (OR) of 75 (P < 0.003). CONCLUSION: This first study in Indian population shows that genotype AA polymorphism of SNP rs4236 of MGP gene was found to be significant risk factor for renal stone disease. Studies with larger sample size may be needed to confirm this finding and elucidate the exact OR.