Aniridics with PAX-6 Mutations Display Increased Insulin Resistance Compared to Relatives Without Aniridia
Poster #: 087
Session/Time: B
Author:
Andrew Phong Huynh, BS
Mentor:
Peter A. Netland, MD, PhD
Research Type: Clinical Research
Abstract
INTRODUCTION:
Aniridia is a rare disorder (incidence between 1 : 64000 and 1 : 100000) due to mutations in the PAX6, a highly conserved regulatory transcription factor. Mutations can be sporadic or familial, with lethal consequences for homozygous mutations. PAX6 plays a key role in the development of the eyes, pancreas, and brain. Ocular complications are primarily characterized by iris and foveal hypoplasia, and secondary complications can include keratopathy, glaucoma, cataract, and dry eye disease. Mice models have found links between PAX6 mutations and impaired glucose metabolism. In this study, we aim to explore the links between aniridia and human metabolism, with a focus on pro-insulinemia.
METHODS:
This prospective case-control study identified 12 aniridics and 12 controls who were non-aniridic relatives. Recruitment and data collection, including blood draws, demographics, and physical measurements, were conducted at the 2013 Aniridia Foundation International meeting. Blood samples were analyzed for various metabolic markers such as HbA1C, c-peptide, ghrelin, and GLP-1. Quantitative Insulin Sensitivity Check Index (QUICKI), was calculated from fasting glucose and insulin levels and used to assess insulin sensitivity. Statistical analysis was conducted using R.
RESULTS:
Aniridics compared to controls showed a higher C-peptide level, 4.00 ng/ml vs 1.85 ng/ml (p=0.00352). Aniridics also had decreased insulin sensitivity compared to controls (p=0.00422). A QUICKI analysis of overweight or obese aniridics and controls, as defined by the WHO BMI, also showed a statistically significant difference (p=0.0136).
CONCLUSION:
The results confirm with existing literature and animal models that PAX6 plays a key role in human metabolism. PAX6 mutations are one of the few genetic conditions that have been associated with obesity. A deeper understanding of this mechanism could eventually lead to novel therapies.
Aniridia is a rare disorder (incidence between 1 : 64000 and 1 : 100000) due to mutations in the PAX6, a highly conserved regulatory transcription factor. Mutations can be sporadic or familial, with lethal consequences for homozygous mutations. PAX6 plays a key role in the development of the eyes, pancreas, and brain. Ocular complications are primarily characterized by iris and foveal hypoplasia, and secondary complications can include keratopathy, glaucoma, cataract, and dry eye disease. Mice models have found links between PAX6 mutations and impaired glucose metabolism. In this study, we aim to explore the links between aniridia and human metabolism, with a focus on pro-insulinemia.
METHODS:
This prospective case-control study identified 12 aniridics and 12 controls who were non-aniridic relatives. Recruitment and data collection, including blood draws, demographics, and physical measurements, were conducted at the 2013 Aniridia Foundation International meeting. Blood samples were analyzed for various metabolic markers such as HbA1C, c-peptide, ghrelin, and GLP-1. Quantitative Insulin Sensitivity Check Index (QUICKI), was calculated from fasting glucose and insulin levels and used to assess insulin sensitivity. Statistical analysis was conducted using R.
RESULTS:
Aniridics compared to controls showed a higher C-peptide level, 4.00 ng/ml vs 1.85 ng/ml (p=0.00352). Aniridics also had decreased insulin sensitivity compared to controls (p=0.00422). A QUICKI analysis of overweight or obese aniridics and controls, as defined by the WHO BMI, also showed a statistically significant difference (p=0.0136).
CONCLUSION:
The results confirm with existing literature and animal models that PAX6 plays a key role in human metabolism. PAX6 mutations are one of the few genetic conditions that have been associated with obesity. A deeper understanding of this mechanism could eventually lead to novel therapies.