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Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

ABSTRACT: Introduction:Diabetic nephropathy (DN) is the commonest single cause of end-stage renal failure, and dyslipidemia is a critical risk factor in the occurrence of DN. In the light of recent reports emphasizing the importance of angiotensin I-converting enzyme (ACE) in the modulation of plasma lipids, we sought to evaluate the influence of ACE I/D gene polymorphism with dyslipidemia status among type 2 diabetic (T2D) patients with and without nephropathy in the genetic predisposition and the progression to DN. Method:This study comprised of 600 subjects, which include patients with DN, T2D, and healthy controls (HC). Polymerase chain reaction based genotyping of ACE I/D polymorphism was performed and appropriate statistical analysis was done. Results:Out of the 600 subjects, 20 (10%) of the HC, 73 (36.5%) of the T2D group, and 125 (62.5%) of the DN subjects had dyslipidemia. The D allele (0.62) and DD (42.5) genotype frequencies were higher in the DN group in comparison with T2D and HC (P < 0.05). The genotypes also varied among patients with dyslipidemia (?2 5.04; P < 0.05) but not in the non-dyslipidemia group. Under the co-dominant model, DD genotype conferred a risk of 1.26 (P < 0.001) toward DN, whereas the ID genotype offered protection from DN among the dyslipidemic subjects (OR = 0.05; P < 0.01). In addition, genotype-dependent difference was seen in the plasma lipid levels among study groups. A multiple logistic regression analysis revealed male gender, BMI, HbA1c, TG, HDL, and ACE DD genotype as independent risk factors for the development of DN. Conclusion:The study showed a significant predisposing association of ACE DD genotype with DN and protective effect of ID genotype on DN in the dyslipidemia subgroup.

SUBMITTER: Mahwish UN

PROVIDER: S-EPMC7132849 | biostudies-literature | 2020 Mar-Apr

REPOSITORIES: biostudies-literature

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Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

Mahwish Umme Najiya UN Ponnaluri Kamakshi Chaithri KC Heera Babi B Alavala Satish Reddy SR Devi K Rudrama KR Raju Sree Bhushan SB Latha G Suman GS Jahan Parveen P

Indian journal of nephrology 20200207 2

<h4>Introduction</h4>Diabetic nephropathy (DN) is the commonest single cause of end-stage renal failure, and dyslipidemia is a critical risk factor in the occurrence of DN. In the light of recent reports emphasizing the importance of angiotensin I-converting enzyme (ACE) in the modulation of plasma lipids, we sought to evaluate the influence of ACE I/D gene polymorphism with dyslipidemia status among type 2 diabetic (T2D) patients with and without nephropathy in the genetic predisposition and th ...[more]

PMID: 32269430

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Project description:Type 1 diabetes (T1D) increases risk of the development of microvascular complications and cardiovascular disease (CVD). Dyslipidemia is a common risk factor in the pathogenesis of both CVD and diabetic nephropathy (DN), with CVD identified as the primary cause of death in patients with DN. In light of this commonality, we assessed single nucleotide polymorphisms (SNPs) in thirty-seven key genetic loci previously associated with dyslipidemia in a T1D cohort using a case-control design. SNPs (n = 53) were genotyped using Sequenom in 1467 individuals with T1D (718 cases with proteinuric nephropathy and 749 controls without nephropathy i.e. normal albumin excretion). Cases and controls were white and recruited from the UK and Ireland. Association analyses were performed using PLINK to compare allele frequencies in cases and controls. In a sensitivity analysis, samples from control individuals with reduced renal function (estimated glomerular filtration rate<60 ml/min/1.73 m(2)) were excluded. Correction for multiple testing was performed by permutation testing. A total of 1394 samples passed quality control filters. Following regression analysis adjusted by collection center, gender, duration of diabetes, and average HbA1c, two SNPs were significantly associated with DN. rs4420638 in the APOC1 region (odds ratio [OR] = 1.51; confidence intervals [CI]: 1.19-1.91; P = 0.001) and rs1532624 in CETP (OR = 0.82; CI: 0.69-0.99; P = 0.034); rs4420638 was also significantly associated in a sensitivity analysis (P = 0.016) together with rs7679 (P = 0.027). However, no association was significant following correction for multiple testing. Subgroup analysis of end-stage renal disease status failed to reveal any association. Our results suggest common variants associated with dyslipidemia are not strongly associated with DN in T1D among white individuals. Our findings, cannot entirely exclude these key genes which are central to the process of dyslipidemia, from involvement in DN pathogenesis as our study had limited power to detect variants of small effect size. Analysis in larger independent cohorts is required.

Project description:BackgroundDiabetic nephropathy is the most serious complication of diabetes which leads to end-stage renal failure and other complication of diabetes mellitus. Determinants of Diabetic nephropathy are not consistent in different studies and associated factors to chronic complications of diabetes are not specific and there are limited studies specific to diabetic nephropathy. Thus, the aim of this study is to identify determinants of diabetic nephropathy in Ayder Referral Hospital, Northern Ethiopia.MethodsA case-control study was conducted from February 14 to May 8 2016. Diabetic patients who developed nephropathy in the last two years were the cases and diabetic patients free of nephropathy were controls. Cases and controls were identified detailed review of the chronic care follow up chart. Then simple random sampling was used to select sample of 420 (with control to case ratio of 4:1) resulting in 84 cases and 336 controls. Record review and interviewer administered questionnaire were used to collect data. Data was coded and entered in to Epi-Data version 3.1 and then exported to STATA 12 for analysis. Variables with P-values< 0.25 in Bivariate logistic regression were selected for multiple logistic regressions to determine independent determinants of diabetic nephropathy. OR was calculated with 95% CI to show strength of association.ResultThe mean age (±Standard deviation) for the cases and the controls were 52(SD: ±1.34) and 42.4(SD: ±0.8) respectively. In multiple logistic regressions age of patient (AOR: 1.037 95%CI: 1.01-1.064), duration of diabetes after diagnosis (AOR for one year increase: 1.09 95%CI: 1.036-1.15), not-adhered to blood glucose measurement at home (AOR: 6.81 95%CI: 1.15-40.24), having Systolic Hypertension (AOR;2.13 (1.002-4.51), poor glycemic control (AOR;2.71 95%CI: (1.49-4.95), being overweight(AOR;2.7(1.47-4.96) were the independent predictors of diabetic nephropathy.ConclusionIn the light of these findings, targeted interventions should be designed at the follow up clinic to address the risk of developing diabetic nephropathy among the risk groups.

Dataset Information

Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

Publications

Link between ACE I/D Gene Polymorphism and Dyslipidemia in Diabetic Nephropathy: A Case-control Study from Hyderabad, India.

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