TY - JOUR

T1 - IDENTIFICATION OF NOVEL VARIANTS IN THE HEPATOCYTE NUCLEAR FACTOR 1 ALPHA GENE IN SOUTH INDIAN PATIENTS WITH MATURITY ONSET DIABETES OF YOUNG

AU - Radha, V

AU - Ek, J

AU - Anuradha, S

AU - Hansen, T

AU - Pedersen, Oluf

AU - Mohan, V

PY - 2009

Y1 - 2009

N2 - Context: Mutations in the HNF 1A gene are the commonest cause of maturity-onset diabetes of the young (MODY) in most populations. India currently has the largest number of people with diabetes in the world and onset of type 2 diabetes occurs at a younger age with possible overlap with MODY. There is very little data on MODY mutations from India. Objective: The objective was to screen coding and promoter regions of HNF1A gene for mutations in unrelated South Indian subjects in whom a clinical diagnosis of MODY was made. Design: An observational cross-sectional study. Setting: A Diabetes Specialities Centre in Chennai, in southern India. Patients: Ninty-six unrelated south Indian subjects in whom clinical diagnosis of MODY was made were included in the study. The control population comprised of 57 unrelated non-diabetic subjects selected from the Chennai Urban Rural Epidemiology Study (CURES), a study conducted on a representative population (aged >/= 20 years) of Chennai. Results: We identified 9 novel variants comprising 7 mutations(one novel mutation -538G-->C at promoter region and six novel coding region mutations) and 2 polymorphisms in the HNF1A gene. Functional studies revealed reduced transcriptional activity of the HNF1A promoter for two of promoter variants. We also observed co-segregation with diabetes of the Arg263His coding region mutation in 8 members of one MODY family while it was absent in non-diabetic subjects of this family. Conclusion: This study suggests that mutations in HNF1Agene comprise about 9% of clinically diagnosed MODY subjects in S. India and a novel Arg263His mutation cosegregates with MODY in one family.

AB - Context: Mutations in the HNF 1A gene are the commonest cause of maturity-onset diabetes of the young (MODY) in most populations. India currently has the largest number of people with diabetes in the world and onset of type 2 diabetes occurs at a younger age with possible overlap with MODY. There is very little data on MODY mutations from India. Objective: The objective was to screen coding and promoter regions of HNF1A gene for mutations in unrelated South Indian subjects in whom a clinical diagnosis of MODY was made. Design: An observational cross-sectional study. Setting: A Diabetes Specialities Centre in Chennai, in southern India. Patients: Ninty-six unrelated south Indian subjects in whom clinical diagnosis of MODY was made were included in the study. The control population comprised of 57 unrelated non-diabetic subjects selected from the Chennai Urban Rural Epidemiology Study (CURES), a study conducted on a representative population (aged >/= 20 years) of Chennai. Results: We identified 9 novel variants comprising 7 mutations(one novel mutation -538G-->C at promoter region and six novel coding region mutations) and 2 polymorphisms in the HNF1A gene. Functional studies revealed reduced transcriptional activity of the HNF1A promoter for two of promoter variants. We also observed co-segregation with diabetes of the Arg263His coding region mutation in 8 members of one MODY family while it was absent in non-diabetic subjects of this family. Conclusion: This study suggests that mutations in HNF1Agene comprise about 9% of clinically diagnosed MODY subjects in S. India and a novel Arg263His mutation cosegregates with MODY in one family.

U2 - 10.1210/jc.2008-2371

DO - 10.1210/jc.2008-2371

M3 - Journal article

C2 - 19336507

VL - 6

SP - 1959

EP - 1965

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

ER -