Related Experiment Videos
Angiotensin-converting enzyme gene polymorphism and lipid profiles in Kuwaiti children with type 1 diabetes
M Alsaeid1, M A A Moussa, M Z Haider
1Department of Paediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait.
Insights
Angiotensin-converting enzyme (ACE) gene polymorphism influences lipid profiles in Kuwaiti children with type 1 diabetes, particularly the DD genotype. Poor glycemic control and elevated cholesterol contribute to increased lipoprotein(a) levels, suggesting a link to cardiovascular disease risk.
Area of Science:
- Genetics and Cardiovascular Health
- Pediatric Endocrinology
- Molecular Biology
Background:
- Type 1 diabetes in children is associated with dyslipidemia and increased cardiovascular disease (CVD) risk.
- The angiotensin-converting enzyme (ACE) gene polymorphism is implicated in cardiovascular health.
- Understanding the interplay between ACE genotype, lipid profiles, and CVD risk factors in diabetic children is crucial.
Purpose of the Study:
- To investigate the association between ACE gene polymorphism and lipid profiles in Kuwaiti children with type 1 diabetes.
- To explore the relationship between ACE genotypes, lipid parameters, glycated hemoglobin (HbA1c), and cardiovascular risk factors.
- To determine the influence of ACE polymorphism on dyslipidemia and potential CVD risk in this pediatric population.
Main Methods:
- A case-control study involving 125 children with type 1 diabetes and 125 age- and gender-matched healthy controls.
- Evaluation of serum lipids (total cholesterol, HDL, LDL-c, TG, apo A1, apo B, Lp(a)) and HbA1c.
- Analysis of ACE gene polymorphism (II, ID, DD genotypes) and its correlation with clinical and biochemical parameters.
Main Results:
- Genotype distributions were similar between diabetic children and controls, with a higher frequency of the DD genotype.
- Diabetic children with the DD genotype exhibited significantly higher total cholesterol, HDL, and apo A1 levels.
- Elevated Lp(a) levels were associated with a family history of CVD and correlated with HbA1c, particularly in cases of poor glycemic control. Logistic regression identified increased TC and poor glycemic control as significant predictors of elevated Lp(a).
Conclusions:
- ACE polymorphism may partially contribute to CVD risk in children with type 1 diabetes, mediated by factors like poor glycemic control, total cholesterol, and Lp(a) levels.
- The DD genotype is associated with altered lipid profiles in diabetic children.
- Further longitudinal studies with larger sample sizes are recommended to elucidate the role of ACE polymorphism in CVD development in this population.
Methods:
We studied angiotensin-converting enzyme (ACE) gene polymorphism and lipid profiles in Kuwaiti children with uncomplicated type 1 diabetes. A total of 125 children with type 1 diabetes were matched in a case-control study on age and gender to 125 non-diabetic children as controls. Serum lipids (total cholesterol, TC; high-density lipoprotein cholesterol, HDL; low-density lipoprotein cholesterol, LDL-c; triglycerides, TG; apolipoprotein A1 and B, apo A1 and B; lipoprotein(a), Lp(a)); and glycated hemoglobin, HbA1c were evaluated according to ACE genotypes.
Results:
Genotype distributions were found to be similar in cases [ACE insertion/insertion (II) 9.6%, ACE insertion/deletion (ID) 38.4%, ACE deletion/deletion (DD) 52.0%], and controls (II 8.8%, ID 43.2%, DD 48.0%), and were characterized by higher frequencies of DD, ID, and lower frequencies of II. Diabetic children with DD genotype showed significantly higher levels of TC (p < 0.01), HDL (p < 0.001), and apo A1 (p < 0.001) than controls. There was a higher proportion of diabetic children with family history of cardiovascular disease (CVD) in the DD genotype group (51.9%) than those with II genotype group (11.1%) (p < 0.001). Also, there was a significant increase in the frequency of diabetic children with Lp(a) > 30 mg/dL in children with a family history of CVD (p = 0.008). Lp(a) levels were correlated with HbA1c in the diabetic group (r = 0.239, p = 0.019), but when patients with poor glycemic control (HbA1c > 9%) were excluded, the significant correlation disappeared (r = 0.127, p = 0.381). After adjusting confounding between variables, the logistic regression analysis showed that the two significantly related variables with the rise in Lp(a) were increasing TC level and poor glycemic control.
Conclusions:
In children with type 1 diabetes, the role of ACE polymorphism as a probable contributor to CVD seems to be partially mediated through other factors such as poor glycemic control, TC, and Lp(a) level. A longitudinal study is recommended with a larger number of patients in each ACE genotype group in order to assess such associations.
Related Concept Videos
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Type II Diabetes I: Introduction
Pharmacogenetics of Drug Metabolism: Overview
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenomics: Identification of New Drug Targets