Effect of angiotensin converting enzyme gene I/D polymorphism in patients with metabolic syndrome in North Indian population

Background Numerous studies have investigated the effect of angiotensin converting enzyme （ACE） gene I/D polymorphism and various cardiovascular risk factors in different populations with varied results. Currently, the association of ACE gene polymorphism with metabolic syndrome has not been studied in North Indians. While studies assessing the effect with polymorphism on each of the components of metabolic syndrome separately are present, data regarding the metabolic syndrome per se are sparse. The present study evaluated the effect of ACE gene I/D polymorphism in patients with metabolic syndrome in North Indian population at a tertiary care centre. Methods Fifty subjects, with thirty cases of metabolic syndrome （NCEP/ATP III guidelines, 2004） and twenty age and gender matched healthy controls were chosen. Detailed history was reviewed and clinical examination of the subjects was carried out. Relevant investigations including blood glucose （fasting and post prandial）, blood urea, serum creatinine and serum lipids were done. DNA of cases and controls was analysed for I/D polymorphism using polymerase chain reaction. Results D/D genotype was more frequent in patients with metabolic syndrome as compared with healthy controls （P 〈0.05）. Systolic blood pressure （SBP） and diastolic blood pressure （DBP） was significantly higher in the D/D genotype than I/D and I/I genotypes （P 〈0.05）. Our study also showed positive association between obesity, fasting blood glucose and ACE gene polymorphism while no association was found with triglycerides and high density lipoprotein cholesterol. The I/I group was significantly associated with waist circumference and fasting blood glucose （P 〈0.05）. Conclusion Our study clearly showed that metabolic syndrome was associated with ACE gene polymorphism. However due to less number of subjects in the study further studies are needed to corroborate our results.

Disease Progression, Response to ACEI/ATRA Therapy and Influence of ACE Gene in IgA Nephritis

Various studies have shown that angiotensin-converting enzyme （ACE） gene insertion/deletion （ID） polymorphism may play a role in the progression to end stage renal failure （ESRF） in patients with IgA nephritis （IgAN）. In this randomized controlled trial, patients were followed up for 5 years to determine their long-term renal outcome to ACEI/ATRA therapy and to ascertain if their ACE gene profile could play a role in determining their response to therapy. Seventy-five patients with IgAN were enlisted. Thirty-seven were on ACEI/ATRA therapy for 62 ± 5 months and thirty-eight were untreated and served as controls. All patients had their ACE gene ID polymorphism genotyped. Compared to controls, treated patients had lower serum creatinine （p 〈 0.001）, lower proteinuria （p 〈 0.002） and fewer numbers progressing to ESRF （p 〈 0.002）. Among patients with genotype II, there were less ESRF in the treatment group when compared to the untreated control group （p 〈 0.02）. The advantage of therapy was not seen in patients with ID or DD genotypes. ACEI/ATRA therapy was found to be effective in retarding disease progression in IgAN with years to ESRF significantly extended in patients at all levels of renal function, including patients whose outcome were ESRF. Genotyping showed better response to therapy only for those with genotype Ⅱ. The common mechanism is probably through lower levels of ACE, glomerular pressure and proteinuria resulting in reduced renal damage and retardation of progression to ESRF. Cellular ＆ Molecular Immunology.