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Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population
Polymorphic variations in the neurogenic differentiation-1, neurogenin-3, and hepatocyte nuclear factor-1alpha genes contribute to glucose intolerance in a South Indian population
- Source :
- Diabetes. 53(8)
- Publication Year :
- 2004
-
Abstract
- The neurogenic differentiation-1 (NEUROD1), neurogenin-3 (NEUROG3), and hepatic nuclear factor-1α (TCF1) genes are interacting transcription factors implicated in controlling islet cell development and insulin secretion. Polymorphisms of these genes (Ala45Thr [NEUROD1], Ser199Phe [NEUROG3], and Ala98Val [TCF1]) have been postulated to influence the development of type 2 diabetes. We have investigated the role and interaction between these variants using PCR/restriction fragment–length polymorphism assays in 454 subjects recruited as part of a population survey in South India. Additionally, 97 South Indian parent-offspring trios were studied. Polymorphisms of all three genes were associated with either fasting blood glucose (FBG) and/or 2-h blood glucose (BG) in either the total dataset or when restricted to a normoglycemic population. A monotonically increasing effect, dependent on the total number of risk-associated alleles carried, was observed across the whole population (P < 0.0001 for FBG and 2-h BG), raising FBG by a mean of 2.9 mmol/l and 2-h BG by a mean of 4.3 mmol/l. Similarly, an ascending number of the same risk alleles per subject increased the likelihood of type 2 diabetes (P = 0.002). In conclusion, we observed a combined effect of variations in NEUROD1, NEUROG3, and TCF1 in contributing to overall glucose intolerance in a South Indian population.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Population
India
Nerve Tissue Proteins
Type 2 diabetes
Biology
Internal medicine
Diabetes mellitus
Glucose Intolerance
Internal Medicine
medicine
Basic Helix-Loop-Helix Transcription Factors
Ethnicity
Humans
Hepatocyte Nuclear Factor 1-alpha
Allele
education
Gene
education.field_of_study
geography
geography.geographical_feature_category
Polymorphism, Genetic
Nuclear Proteins
medicine.disease
Islet
DNA-Binding Proteins
Hepatocyte nuclear factors
Endocrinology
Amino Acid Substitution
Diabetes Mellitus, Type 2
NEUROD1
Hepatocyte Nuclear Factor 1
Trans-Activators
Transcription Factors
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 53
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....cd341af21699eaca7e41dc2fa2ce78c4