Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes

Research output: Contribution to journalJournal articleResearchpeer-review

Standard

Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes. / Gjesing, Anette P; Nielsen, Aneta A; Brandslund, Ivan; Christensen, Cramer; Sandbæk, Anneli; Jørgensen, Torben; Witte, Daniel; Bonnefond, Amélie; Froguel, Phillippe; Hansen, Torben; Pedersen, Oluf.

In: B M C Medical Genetics, Vol. 12, 01.01.2011, p. 99.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Gjesing, AP, Nielsen, AA, Brandslund, I, Christensen, C, Sandbæk, A, Jørgensen, T, Witte, D, Bonnefond, A, Froguel, P, Hansen, T & Pedersen, O 2011, 'Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes', B M C Medical Genetics, vol. 12, pp. 99. https://doi.org/10.1186/1471-2350-12-99

APA

Gjesing, A. P., Nielsen, A. A., Brandslund, I., Christensen, C., Sandbæk, A., Jørgensen, T., ... Pedersen, O. (2011). Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes. B M C Medical Genetics, 12, 99. https://doi.org/10.1186/1471-2350-12-99

Vancouver

Gjesing AP, Nielsen AA, Brandslund I, Christensen C, Sandbæk A, Jørgensen T et al. Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes. B M C Medical Genetics. 2011 Jan 1;12:99. https://doi.org/10.1186/1471-2350-12-99

Author

Gjesing, Anette P ; Nielsen, Aneta A ; Brandslund, Ivan ; Christensen, Cramer ; Sandbæk, Anneli ; Jørgensen, Torben ; Witte, Daniel ; Bonnefond, Amélie ; Froguel, Phillippe ; Hansen, Torben ; Pedersen, Oluf. / Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes. In: B M C Medical Genetics. 2011 ; Vol. 12. pp. 99.

Bibtex

@article{234bbf8b646e4c75bedfa919f75b11e2,
title = "Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes",
abstract = "Background: Single nucleotide polymorphisms (SNPs) within the gene encoding Hexokinase 1 (HK1) are associated with changes in glycated haemoglobin (HbA1c) levels. Our aim was to investigate the effect of HK1 rs7072268 on measures of glucose- and lipid-metabolism in a Danish non-diabetic population and combine the outcome of these analyses in a meta-analysis with previously published results. Furthermore, our aim was to perform a type 2 diabetes case-control analysis and meta-analysis with two previous case-control studies. Methods: SNP rs7072268 was genotyped in 9,724 Danes. The quantitative trait study included 5,604 non-diabetic individuals from the Inter99 cohort. The case-control study included 4,449 glucose tolerant individuals and 3,398 patients with type 2 diabetes. Meta-analyses on quantitative traits included 24,560 Caucasian individuals and 30,802 individuals were included in the combined analysis of present and previous type 2 diabetes case-control studies. Results: Using an additive model, we confirmed that the T-allele of rs7072268 associates with increased HbA1c of 0.6{\%} (CI: 0.4 - 0.9), p = 3*10-7 per allele. The same allele associated with an increased area under the curve (AUC) for glucose of 5.0 mmol/l*min (0.1 - 10.0), p = 0.045 following an oral glucose tolerance test (OGTT) and increased fasting levels of cholesterol of 0.06 mmol/l (0.03 - 1.0), p = 0.001 and triglycerides of 2.0{\%} (0.2 - 3.8), p = 0.03 per allele in the same study sample of non-diabetic individuals from the Inter99 cohort. However, the T-allele did not show any association with estimates of insulin release or insulin sensitivity neither in Inter99 nor in combined analyses. The prevalence of type 2 diabetes was increased among carriers of the rs7072268 T-allele both in the Danish study-population with an OR of 1.11 (1.02-1.21) and in a meta-analysis including the two additional sample sets with an OR of 1.06 (1.02-1.11). However, after Bonferroni correction the T-allele only remained associated to HbA1c and fasting cholesterol. Conclusions: The present study provides suggestive evidence of an association of the rs7072268 T-allele in HK1 with increased AUC glucose following an OGTT in non-diabetic individuals and a nominal association with type 2 diabetes prior to Bonferro",
keywords = "Case-Control Studies, Denmark, Diabetes Mellitus, Type 2, Genome-Wide Association Study, Genotype, Glucose Tolerance Test, Hemoglobin A, Glycosylated, Hexokinase, Humans, Models, Statistical, Polymorphism, Single Nucleotide, Prevalence",
author = "Gjesing, {Anette P} and Nielsen, {Aneta A} and Ivan Brandslund and Cramer Christensen and Anneli Sandb{\ae}k and Torben J{\o}rgensen and Daniel Witte and Am{\'e}lie Bonnefond and Phillippe Froguel and Torben Hansen and Oluf Pedersen",
year = "2011",
month = "1",
day = "1",
doi = "10.1186/1471-2350-12-99",
language = "English",
volume = "12",
pages = "99",
journal = "B M C Medical Genetics",
issn = "1471-2350",
publisher = "BioMed Central Ltd.",

}

RIS

TY - JOUR

T1 - Studies of a genetic variant in HK1 in relation to quantitative metabolic traits and to the prevalence of type 2 diabetes

AU - Gjesing, Anette P

AU - Nielsen, Aneta A

AU - Brandslund, Ivan

AU - Christensen, Cramer

AU - Sandbæk, Anneli

AU - Jørgensen, Torben

AU - Witte, Daniel

AU - Bonnefond, Amélie

AU - Froguel, Phillippe

AU - Hansen, Torben

AU - Pedersen, Oluf

PY - 2011/1/1

Y1 - 2011/1/1

N2 - Background: Single nucleotide polymorphisms (SNPs) within the gene encoding Hexokinase 1 (HK1) are associated with changes in glycated haemoglobin (HbA1c) levels. Our aim was to investigate the effect of HK1 rs7072268 on measures of glucose- and lipid-metabolism in a Danish non-diabetic population and combine the outcome of these analyses in a meta-analysis with previously published results. Furthermore, our aim was to perform a type 2 diabetes case-control analysis and meta-analysis with two previous case-control studies. Methods: SNP rs7072268 was genotyped in 9,724 Danes. The quantitative trait study included 5,604 non-diabetic individuals from the Inter99 cohort. The case-control study included 4,449 glucose tolerant individuals and 3,398 patients with type 2 diabetes. Meta-analyses on quantitative traits included 24,560 Caucasian individuals and 30,802 individuals were included in the combined analysis of present and previous type 2 diabetes case-control studies. Results: Using an additive model, we confirmed that the T-allele of rs7072268 associates with increased HbA1c of 0.6% (CI: 0.4 - 0.9), p = 3*10-7 per allele. The same allele associated with an increased area under the curve (AUC) for glucose of 5.0 mmol/l*min (0.1 - 10.0), p = 0.045 following an oral glucose tolerance test (OGTT) and increased fasting levels of cholesterol of 0.06 mmol/l (0.03 - 1.0), p = 0.001 and triglycerides of 2.0% (0.2 - 3.8), p = 0.03 per allele in the same study sample of non-diabetic individuals from the Inter99 cohort. However, the T-allele did not show any association with estimates of insulin release or insulin sensitivity neither in Inter99 nor in combined analyses. The prevalence of type 2 diabetes was increased among carriers of the rs7072268 T-allele both in the Danish study-population with an OR of 1.11 (1.02-1.21) and in a meta-analysis including the two additional sample sets with an OR of 1.06 (1.02-1.11). However, after Bonferroni correction the T-allele only remained associated to HbA1c and fasting cholesterol. Conclusions: The present study provides suggestive evidence of an association of the rs7072268 T-allele in HK1 with increased AUC glucose following an OGTT in non-diabetic individuals and a nominal association with type 2 diabetes prior to Bonferro

AB - Background: Single nucleotide polymorphisms (SNPs) within the gene encoding Hexokinase 1 (HK1) are associated with changes in glycated haemoglobin (HbA1c) levels. Our aim was to investigate the effect of HK1 rs7072268 on measures of glucose- and lipid-metabolism in a Danish non-diabetic population and combine the outcome of these analyses in a meta-analysis with previously published results. Furthermore, our aim was to perform a type 2 diabetes case-control analysis and meta-analysis with two previous case-control studies. Methods: SNP rs7072268 was genotyped in 9,724 Danes. The quantitative trait study included 5,604 non-diabetic individuals from the Inter99 cohort. The case-control study included 4,449 glucose tolerant individuals and 3,398 patients with type 2 diabetes. Meta-analyses on quantitative traits included 24,560 Caucasian individuals and 30,802 individuals were included in the combined analysis of present and previous type 2 diabetes case-control studies. Results: Using an additive model, we confirmed that the T-allele of rs7072268 associates with increased HbA1c of 0.6% (CI: 0.4 - 0.9), p = 3*10-7 per allele. The same allele associated with an increased area under the curve (AUC) for glucose of 5.0 mmol/l*min (0.1 - 10.0), p = 0.045 following an oral glucose tolerance test (OGTT) and increased fasting levels of cholesterol of 0.06 mmol/l (0.03 - 1.0), p = 0.001 and triglycerides of 2.0% (0.2 - 3.8), p = 0.03 per allele in the same study sample of non-diabetic individuals from the Inter99 cohort. However, the T-allele did not show any association with estimates of insulin release or insulin sensitivity neither in Inter99 nor in combined analyses. The prevalence of type 2 diabetes was increased among carriers of the rs7072268 T-allele both in the Danish study-population with an OR of 1.11 (1.02-1.21) and in a meta-analysis including the two additional sample sets with an OR of 1.06 (1.02-1.11). However, after Bonferroni correction the T-allele only remained associated to HbA1c and fasting cholesterol. Conclusions: The present study provides suggestive evidence of an association of the rs7072268 T-allele in HK1 with increased AUC glucose following an OGTT in non-diabetic individuals and a nominal association with type 2 diabetes prior to Bonferro

KW - Case-Control Studies

KW - Denmark

KW - Diabetes Mellitus, Type 2

KW - Genome-Wide Association Study

KW - Genotype

KW - Glucose Tolerance Test

KW - Hemoglobin A, Glycosylated

KW - Hexokinase

KW - Humans

KW - Models, Statistical

KW - Polymorphism, Single Nucleotide

KW - Prevalence

U2 - 10.1186/1471-2350-12-99

DO - 10.1186/1471-2350-12-99

M3 - Journal article

VL - 12

SP - 99

JO - B M C Medical Genetics

JF - B M C Medical Genetics

SN - 1471-2350

ER -

ID: 35314264