TY - JOUR

T1 - The effect of two frequent amino acid variants of the hepatocyte nuclear factor-1α gene on estimates of the pancreatic β-cell function in Caucasian glucosetolerant first-degree relatives of type 2 diabetic patients

AU - Urhammer, Søren A.

AU - Møller, Ann Merete

AU - Nyholm, Birgit

AU - Ekstrøm, Claus T.

AU - Eiberg, Hans

AU - Clausen, Jesper O.

AU - Hansen, Torben

AU - Pedersen, Oluf

AU - Schmitz, Ole

PY - 1998/11/20

Y1 - 1998/11/20

N2 - The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

AB - The objective of the present study was to investigate whether the frequent amino acid polymorphisms, Ile/Leu27 and Ser/Asn487, of the hepatocyte nuclear factor-1α gene were associated with alterations in glucose-induced serum C-peptide and serum insulin responses among glucose- tolerant first-degree relatives of type 2 diabetic patients. The study comprised 2 independent Danish cohorts. Among 74 unrelated type 2 diabetic relatives, 12 homozygous carriers of the Ile/Leu27 polymorphism had a 32% decrease in the 30-min serum C-peptide level (P = 0.01), as well as a 39% decrease in the 30-min serum insulin level (P = 0.02) during an oral glucose tolerance test. Ten homozygous carriers of the Ile/Leu27 variant did, however, not differ from wildtype carriers, with respect to the acute circulating insulin and serum C-peptide responses during an iv glucose tolerance test in the same study cohort. In a larger (more than 3-fold) study group of 230 glucose tolerant offspring of 62 type 2 diabetic probands, 33 homozygous carriers of the Ile/Leu27 variant did not differ, with respect to either serum insulin and serum C-peptide levels during an oral glucose tolerance test or acute serum insulin and serum C-peptide responses during an iv glucose tolerance test. We therefore consider the former positive finding as a statistical type I error. There were no differences in the above mentioned variables between carriers of the Ser/Asn487 polymorphism and wild- type carriers within any of the 2 study populations. Nor did carriers of combined genotypes, i.e. carriers of both the Ile/Leu27 and the Ser/Asn487 variants, show any associations with the examined variables. In conclusion, the Ile/Leu27 and Set/Ash487 polymorphisms of the hepatocyte nuclear factor- 1α gene have apparently no major impact on the pancreatic β-cell function, after an oral and iv glucose challenge, in Caucasian first-degree relatives of type 2 diabetic patients.

UR - http://www.scopus.com/inward/record.url?scp=0031732687&partnerID=8YFLogxK

M3 - Journal article

C2 - 9814481

AN - SCOPUS:0031732687

VL - 83

SP - 3992

EP - 3995

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 11

ER -