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The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort.
Diabetes Metab Res Rev. 2009 Feb; 25(2):156-62.DM

Abstract

BACKGROUND

In the present study, we aimed to validate the type 2 diabetes (T2DM) susceptibility alleles identified in the first genome-wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837). Furthermore, we investigated quantitative metabolic risk phenotypes of these two variants for association with three key components of the insulin metabolism: insulin secretion, insulin sensitivity and insulin degradation.

METHODS

Two HHEX polymorphisms were genotyped in 1026 subjects from the German MESYBEPO cohort. Complete OGTT data were available for a subset of 420 with normal glucose tolerance (NGT), 282 with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) and 146 diabetic subjects.

RESULTS

We validated association of both HHEX polymorphisms with T2DM. In the non-diabetic subcohort including NGT and IFG/IGT subjects, the risk alleles of rs7923837 and rs1111875 were significantly associated with decreased first and second phases of insulin secretion and lower insulinogenic index after oral glucose loading. In healthy, normal glucose-tolerant subjects, the same association of HHEX SNP rs1111875 with OGTT-derived phases of insulin secretion were detectable, however, rs7923837 was only weakly associated with reduced insulinogenic index. For both polymorphisms, no significant correlations with insulin sensitivity were obtained. Reduced insulin clearance was also observed in heterozygous carriers of rs1111875.

CONCLUSIONS

We validated the association of polymorphisms of the HHEX gene with T2DM in the MESYBEPO cohort. Importantly, variations within the HHEX gene conferred the impaired insulin secretion and changes of insulin degradation but no alteration in insulin sensitivity in carriers of risk alleles.

Authors+Show Affiliations

Department of Clinical Nutrition, German Institute of Human Nutrition, Potsdam, Germany. olga.pivovarova@dife.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19117022

Citation

Pivovarova, Olga, et al. "The Influence of Genetic Variations in HHEX Gene On Insulin Metabolism in the German MESYBEPO Cohort." Diabetes/metabolism Research and Reviews, vol. 25, no. 2, 2009, pp. 156-62.
Pivovarova O, Nikiforova VJ, Pfeiffer AF, et al. The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes Metab Res Rev. 2009;25(2):156-62.
Pivovarova, O., Nikiforova, V. J., Pfeiffer, A. F., & Rudovich, N. (2009). The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. Diabetes/metabolism Research and Reviews, 25(2), 156-62. https://doi.org/10.1002/dmrr.926
Pivovarova O, et al. The Influence of Genetic Variations in HHEX Gene On Insulin Metabolism in the German MESYBEPO Cohort. Diabetes Metab Res Rev. 2009;25(2):156-62. PubMed PMID: 19117022.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The influence of genetic variations in HHEX gene on insulin metabolism in the German MESYBEPO cohort. AU - Pivovarova,Olga, AU - Nikiforova,Victoria J, AU - Pfeiffer,Andreas F H, AU - Rudovich,Natalia, PY - 2009/1/1/entrez PY - 2009/1/1/pubmed PY - 2009/5/16/medline SP - 156 EP - 62 JF - Diabetes/metabolism research and reviews JO - Diabetes Metab. Res. Rev. VL - 25 IS - 2 N2 - BACKGROUND: In the present study, we aimed to validate the type 2 diabetes (T2DM) susceptibility alleles identified in the first genome-wide association study in the hematopoietically expressed homeobox protein (HHEX) gene region (rs1111875 and rs7923837). Furthermore, we investigated quantitative metabolic risk phenotypes of these two variants for association with three key components of the insulin metabolism: insulin secretion, insulin sensitivity and insulin degradation. METHODS: Two HHEX polymorphisms were genotyped in 1026 subjects from the German MESYBEPO cohort. Complete OGTT data were available for a subset of 420 with normal glucose tolerance (NGT), 282 with impaired glucose tolerance/impaired fasting glucose (IGT/IFG) and 146 diabetic subjects. RESULTS: We validated association of both HHEX polymorphisms with T2DM. In the non-diabetic subcohort including NGT and IFG/IGT subjects, the risk alleles of rs7923837 and rs1111875 were significantly associated with decreased first and second phases of insulin secretion and lower insulinogenic index after oral glucose loading. In healthy, normal glucose-tolerant subjects, the same association of HHEX SNP rs1111875 with OGTT-derived phases of insulin secretion were detectable, however, rs7923837 was only weakly associated with reduced insulinogenic index. For both polymorphisms, no significant correlations with insulin sensitivity were obtained. Reduced insulin clearance was also observed in heterozygous carriers of rs1111875. CONCLUSIONS: We validated the association of polymorphisms of the HHEX gene with T2DM in the MESYBEPO cohort. Importantly, variations within the HHEX gene conferred the impaired insulin secretion and changes of insulin degradation but no alteration in insulin sensitivity in carriers of risk alleles. SN - 1520-7560 UR - https://www.unboundmedicine.com/medline/citation/19117022/The_influence_of_genetic_variations_in_HHEX_gene_on_insulin_metabolism_in_the_German_MESYBEPO_cohort_ L2 - https://doi.org/10.1002/dmrr.926 DB - PRIME DP - Unbound Medicine ER -