Serum amino acids in patients with mutations in the hepatocyte nuclear factor-1 alpha gene

TY - JOUR

T1 - Serum amino acids in patients with mutations in the hepatocyte nuclear factor-1 alpha gene

AU - Stride, A.

AU - Pearson, E. R.

AU - Brown, A.

AU - Gooding, K.

AU - Castleden, H. A. J.

AU - Hattersley, A. T.

PY - 2004/8

Y1 - 2004/8

N2 - Aims: Knockout mice lacking both copies of the hepatocyte nuclear factor 1 (HNF1) gene have altered serum levels of amino acids and generalized amino-aciduria. The aim of our study was to test whether alterations in serum amino acid levels were found in patients with mutations in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene compared with controls.Methods: Fasting serum from 20 patients with HNF-1α mutations and 20 age, sex and body mass index-matched controls was analysed for 16 amino acids. Means were compared between the two groups and Z scores calculated.Results: There was no significant difference between patients with HNF-1α mutations and controls in serum levels of phenylalanine, arginine, citrulline or lysine as suggested by knockout mice models. Although serum levels of eight amino acids were different in the two groups, these were not significant after Bonferroni correction.Conclusions: The alterations in serum amino acid levels seen in mice models are not seen in patients with mutations in the HNF-1α gene. This suggests differences in mouse and man in the regulation of amino acid transport and has not provided us with a phenotypic marker to use before confirmatory genetic testing.

AB - Aims: Knockout mice lacking both copies of the hepatocyte nuclear factor 1 (HNF1) gene have altered serum levels of amino acids and generalized amino-aciduria. The aim of our study was to test whether alterations in serum amino acid levels were found in patients with mutations in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene compared with controls.Methods: Fasting serum from 20 patients with HNF-1α mutations and 20 age, sex and body mass index-matched controls was analysed for 16 amino acids. Means were compared between the two groups and Z scores calculated.Results: There was no significant difference between patients with HNF-1α mutations and controls in serum levels of phenylalanine, arginine, citrulline or lysine as suggested by knockout mice models. Although serum levels of eight amino acids were different in the two groups, these were not significant after Bonferroni correction.Conclusions: The alterations in serum amino acid levels seen in mice models are not seen in patients with mutations in the HNF-1α gene. This suggests differences in mouse and man in the regulation of amino acid transport and has not provided us with a phenotypic marker to use before confirmatory genetic testing.

KW - Hepatocyte nuclear factor-1 alpha

KW - Maturity-onset diabetes of the young

KW - MODY

KW - Phenotypic markers

KW - Phenylalanine

UR - https://www.scopus.com/pages/publications/3843061389

U2 - 10.1111/j.1464-5491.2004.01107.x

DO - 10.1111/j.1464-5491.2004.01107.x

M3 - Article

C2 - 15270800

AN - SCOPUS:3843061389

SN - 0742-3071

VL - 21

SP - 928

EP - 930

JO - Diabetic Medicine

JF - Diabetic Medicine

IS - 8

ER -