A prevalent amino acid polymorphism at codon 98 (Ala98Val) of the hepatocyte nuclear factor-1alpha is associated with maturity-onset diabetes of the young and younger age at onset of type 2 diabetes in Asian Indians.
OBJECTIVE
Among Europeans, mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene are associated with the most common form of maturity-onset diabetes of the young (MODY)3. In Asian Indians, type 2 diabetes occurs earlier and often overlaps with MODY, but the genetics of the latter are unknown. The aim of this study was to estimate the prevalence of Ala98Val polymorphism of the HNF1alpha gene in different types of diabetes in Asian Indians.


METHODS
Genotyping of Ala98Val was done by the PCR-restriction fragment-length polymorphism method in the following groups: 1) MODY, defined as non-insulin-dependent diabetes (age at onset <25 years) and vertical transmission of diabetes through at least three generations (n = 122); 2) very-early-onset type 2 diabetes (age at onset <25 years) without family history (n = 23); 3) early-onset type 2 diabetes (age at onset between 26 and 40 years, n = 171); 4) late-onset type 2 diabetes (age at onset >40 years, n = 133); 5) type 1 diabetes (n = 150); and 6) normal glucose tolerance (n = 130). The frequency of the Val genotypes was compared in the diabetic and control groups.


RESULTS
The frequency of the Val allele was significantly higher in MODY patients (P = 0.0013) compared with control groups. Furthermore, in the total group of patients with type 2-like diabetes (groups 1-4), the Val allele was associated with an earlier diagnosis of diabetes (P = 0.0002).


CONCLUSIONS
Among Asian Indians, the Ala98Val polymorphism of HNF1alpha gene is associated with MODY and with earlier age at onset of type 2 diabetes.
Anuradha
Shekher
S
Dr. Mohans' MV Diabetes Specialties Centre & Madras Diabetes Research Foundation, Gopalapuram, Chennai, India.
Radha
Venkatesan
V
Deepa
Raj
R
Hansen
Torben
T
Carstensen
Bendix
B
Pedersen
Oluf
O
Mohan
Viswanathan
V
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D017668:Age of Onset; D044466:Asian People / Q000235:genetics* / Q000706:statistics & numerical data; D002648:Child; D003924:Diabetes Mellitus, Type 2 / Q000208:ethnology* / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000208:ethnology; D051538:Hepatocyte Nuclear Factor 1-alpha / Q000235:genetics*; D006801:Humans; D007194:India / Q000453:epidemiology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
D051538:Hepatocyte Nuclear Factor 1-alpha