ABSTRACT
To determine the sequence variant of TLL1 gene [rs1503298, T > C] in three British cohorts [PREDICT, UDACS and ED] of patients with type-2 Diabetes mellitus [T2DM] in order to assess its association with coronary heart disease [CHD]. Analytical study. UCL, London, UK. Participants were genotyped in 2011-2012 for TLL1 SNP. Samples and related information were previously collected in 2001-2003 for PREDICT, and in 2001-2002 for UDACS and ED groups. Patients included in PREDICT [n=600], UDACS [n=1020] and ED [n=1240] had Diabetes. TLL1 SNP [rs1503298, T > C] was genotyped using TaqMan technology. Allele frequencies were compared using c2 test, and tested for Hardy-Weinberg equilibrium. The risk of disease was assessed from Odds ratios [OR] with 95% Confidence Intervals [95% CI]. Moreover, for the PREDICT cohort, the SNP association was tested with Coronary Artery Calcification [CAC] scores. No significant association was found for this SNP with CHD or CAC scores in these cohorts. This SNP could not be confirmed as a risk factor for CHD in T2DM patients. However, the low power of thesmall sample size available is a limitation to the modest effect on risk. Further studies in larger samples would be useful
ABSTRACT
Diabetes mellitus is a multifactorial disorder of hyperglycemia caused by a combination of biochemical, molecular and genetic factors, which leads to the dysfunction of various organs including kidneys
Diabetic nephropathy [DN] is one of the microvascular complications of diabetes that results due to poor glycemic control. Several molecular and biochemical pathways have been implicated in the pathogenesis of DN
Of these, the Renin Angiotensin Aldosterone System [RAAS] is considered as a key pathway. RAAS involves various subsystems which contribute to the development of DN
Mutations in several genes of the RAAS pathway have been associated with the development of DN
These genes or their products present them as therapeutic targets for potent drugs to control or prevent DN, and development of new drugs for targeting the RAAS
Drugs in use for DN are mainly the Angiotensin Converting Enzyme [ACE] inhibitors, Angiotensin Receptors Blockers [ARE] and renin inhibitors which play important roles in reducing DN
Hence, the present review is focused on the pathophysiology and genetic factors for DN by exploring the RAAS pathway and emphasizing the benefits of blocking this pathway to control and prevent DN