RGD Reference Report - Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians. - Rat Genome Database

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Genetic variability of procolipase associates with altered insulin secretion in non-diabetic Caucasians.

Authors: Weyrich, P  Albet, S  Lammers, R  Machicao, F  Fritsche, A  Stefan, N  Haring, HU 
Citation: Weyrich P, etal., Exp Clin Endocrinol Diabetes. 2009 Feb;117(2):83-7. Epub 2008 Aug 25.
RGD ID: 2314626
Pubmed: PMID:18726866   (View Abstract at PubMed)
DOI: DOI:10.1055/s-2008-1078733   (Journal Full-text)

AIMS: Procolipase (CLPS) is secreted from the exocrine pancreas into the gastrointestinal tract and becomes proteolytically cleaved into colipase and the pentapeptide enterostatin. While colipase is an indispensable cofactor for pancreatic lipase, enterostatin acts as a hormone that inhibits insulin secretion and confers satiety signals to the brain, thereby restricting further food intake in animal models. As both high fat diet and obesity contribute to insulin resistance, we investigated whether genetic variability of CLPS associates with metabolic traits in non-diabetic humans at diabetes risk. METHODS: Tagging single nucleotide polymorphisms (SNPs) in the human CLPS locus on chr6p21.1 were selected using HapMap data. 498 humans, phenotyped for different glucose and lipid metabolic traits, were genotyped by bidirectional sequencing and multivariate linear regression analyses were undertaken. RESULTS: 2 tagging SNPs (rs3748050 in the Kozak sequence: A/G and rs3748051 in intron 1: A/G), covering 100% of CLPS variability including 8 kb of its promoter, were genotyped for association analyses. The minor alleles of both tagging SNPs associated significantly with a reduced insulin secretion (-20.2%, both SNPs) in various estimation models derived from the oral glucose tolerance test (OGTT; rs3748050/51: 30 min C-peptide levels: p=0.001/0.01, insulinogenic index: p=0.02/0.02, AUC C-peptide/AUC glucose: p=0.01/0.01) after adjustment for relevant covariates. No significant associations with fasting total cholesterol (c), HDL-c, LDL-c, triglycerides and free fatty acids were found (all p > 0.11). CONCLUSIONS: CLPS genetic variability associates with insulin secretory function in non-diabetic humans and may represent a novel candidate gene for development of type 2 diabetes.

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Hypoinsulinemia  IAGP 2314626DNA:SNPs: :rs3748050 and rs3748051RGD 
Objects Annotated

Genes (Homo sapiens)
CLPS  (colipase)


Additional Information