PMID- 10690959
OWN - NLM
STAT- MEDLINE
DCOM- 20000306
LR  - 20221207
IS  - 0026-0495 (Print)
IS  - 0026-0495 (Linking)
VI  - 49
IP  - 2
DP  - 2000 Feb
TI  - Molecular scanning analysis of hepatocyte nuclear factor 1alpha (TCF1) gene in 
      typical familial type 2 diabetes in African Americans.
PG  - 280-4
AB  - Type 2 diabetes mellitus (T2DM) is strongly inherited, but the major genes for 
      this disease have been elusive. In contrast, early-onset, autosomal-dominant 
      diabetes results from at least 5 loci, of which hepatocyte nuclear factor 1a 
      (HNF1alpha or TCF1) is the most common cause. Mutations in HNF1alpha also cause 
      later-onset diabetes in some Caucasian populations, but the role of these 
      mutations has not been tested in African American populations. We used a variety 
      of screening methods, including both single-strand conformation polymorphism 
      (SSCP) analysis and dideoxy fingerprint analysis, to search for mutations in 51 
      African American subjects with onset of diabetes before age 50 years. Potential 
      mutations were confirmed by direct sequencing. We identified 21 different 
      variants, of which 11 were unique to African Americans. Four mutations either 
      altered the amino acid sequence (Gly52Ala and Gly574Ser) or were close to a 
      splice site (intron 1 and intron 10). A 5-nucleotide insertion in intron 1 was 
      present in both diabetic members of a small family, but Gly52Ala, Gly574Ser, and 
      the intron 10 mutation did not segregate with diabetes. Gly574Ser was present in 
      2 large families and 5% of controls, all of which appeared to share the same 
      common HNF1alpha haplotype. Surprisingly, radioactive SSCP analysis under 2 
      room-temperature conditions performed as well as methods using fluorescent 
      labeling that were expected to be more sensitive. We conclude that in African 
      American individuals under age 50, variation in the HNF1a gene is common but 
      unlikely to be a significant cause of T2DM.
FAU - Elbein, S C
AU  - Elbein SC
AD  - Division of Endocrinology, Central Arkansas Veterans Health System and University 
      of Arkansas for Medical Sciences, Little Rock, USA.
FAU - Teng, K
AU  - Teng K
FAU - Eddings, K
AU  - Eddings K
FAU - Hargrove, D
AU  - Hargrove D
FAU - Scroggin, E
AU  - Scroggin E
LA  - eng
GR  - DK39301/DK/NIDDK NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Metabolism
JT  - Metabolism: clinical and experimental
JID - 0375267
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HNF1A protein, human)
RN  - 0 (HNF1B protein, human)
RN  - 0 (Hepatocyte Nuclear Factor 1-alpha)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 126548-29-6 (Hepatocyte Nuclear Factor 1)
RN  - 138674-15-4 (Hepatocyte Nuclear Factor 1-beta)
SB  - IM
MH  - Adult
MH  - Black or African American
MH  - Alleles
MH  - *DNA-Binding Proteins
MH  - Diabetes Mellitus, Type 2/*genetics
MH  - Exons/genetics
MH  - Female
MH  - Hepatocyte Nuclear Factor 1
MH  - Hepatocyte Nuclear Factor 1-alpha
MH  - Hepatocyte Nuclear Factor 1-beta
MH  - Humans
MH  - Introns/genetics
MH  - Male
MH  - Middle Aged
MH  - Nuclear Proteins/*genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Transcription Factors/*genetics
EDAT- 2000/02/26 09:00
MHDA- 2000/03/11 09:00
CRDT- 2000/02/26 09:00
PHST- 2000/02/26 09:00 [pubmed]
PHST- 2000/03/11 09:00 [medline]
PHST- 2000/02/26 09:00 [entrez]
AID - S0026-0495(00)91663-9 [pii]
AID - 10.1016/s0026-0495(00)91663-9 [doi]
PST - ppublish
SO  - Metabolism. 2000 Feb;49(2):280-4. doi: 10.1016/s0026-0495(00)91663-9.