The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status

PLoS ONE

Volumn 6, Issue 9, 2011, Pages

  Gjesing, Anette P ^a,b   Vestmar, Marie A ^a,b,d   Jørgensen, Torben ^c,d   Heni, Martin ^e   Holst, Jens J ^d   Witte, Daniel R ^a   Hansen, Torben ^a,b,f   Pedersen, Oluf ^a,b,d,g  

^a STENO DIABETES CENTER   (Denmark)

^b Capital Region   (Denmark)

^c GLOSTRUP UNIVERSITY HOSPITAL   (Denmark)

^d UNIVERSITY OF COPENHAGEN   (Denmark)

^e UNIVERSITY OF TÜBINGEN   (Germany)

^f UNIVERSITY OF SOUTHERN DENMARK   (Denmark)

^g AARHUS UNIVERSITY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOSINE; GLUCAGON; GLUCAGON LIKE PEPTIDE 1; GLUCAGON LIKE PEPTIDE 2; GLUCOSE; GUANINE; INCRETIN; INSULIN; PROPROTEIN CONVERTASE 1; PROTEIN PCSK1; UNCLASSIFIED DRUG;

ADULT; AGE DISTRIBUTION; ARTICLE; BODY COMPOSITION; BODY FAT; CONTROLLED STUDY; DENMARK; FEMALE; GENE FREQUENCY; GENOTYPE; GLUCOSE METABOLISM; HUMAN; INSULIN RESPONSE; MAJOR CLINICAL STUDY; MALE; OBESITY; ORAL GLUCOSE TOLERANCE TEST; PROTEIN VARIANT; SEX DIFFERENCE; TEST MEAL; WAIST CIRCUMFERENCE; WAIST HIP RATIO; ADIPOSE TISSUE; ALLELE; ANTHROPOMETRY; COHORT ANALYSIS; GENE EXPRESSION REGULATION; GENETICS; GLUCOSE TOLERANCE TEST; METABOLISM; METHODOLOGY; MIDDLE AGED; PHYSIOLOGY;

ADIPOSE TISSUE; ADULT; ALLELES; ANTHROPOMETRY; COHORT STUDIES; DENMARK; FEMALE; GENE EXPRESSION REGULATION, ENZYMOLOGIC; GENOTYPE; GLUCOSE; GLUCOSE TOLERANCE TEST; HUMANS; MALE; MIDDLE AGED; OBESITY; PROPROTEIN CONVERTASE 1; SEX FACTORS; WAIST-HIP RATIO;

EID: 80052829855     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0023907     Document Type: Article

References (24)

1. Jansen E, Ayoubi TA, Meulemans SM, Van de Ven WJ, (1995) Neuroendocrine-specific expression of the human prohormone convertase 1 gene. Hormonal regulation of transcription through distinct camp response elements. J Biol Chem 25: 15391-15397.
2. Seidah NG, Benjannet S, Hamelin J, Mamarbachi AM, Basak A, et al. (1999) The subtilisin/kexin family of precursor convertases. Emphasis on pc1, pc2/7b2, pomc and the novel enzyme ski-1. Ann N Y Acad Sci pp. 57-74.
3. Ugleholdt R, Poulsen ML, Holst PJ, Irminger JC, Orskov C, et al. (2006) Prohormone convertase 1/3 is essential for processing of the glucose-dependent insulinotropic polypeptide precursor. J Biol Chem 16: 11050-11057.
4. Jackson RS, Creemers JW, Ohagi S, Raffin-Sanson ML, Sanders L, et al. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 3: 303-306.
5. Jackson RS, Creemers JW, Farooqi IS, Raffin-Sanson ML, Varro A, et al. (2003) Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency. J Clin Invest 10: 1550-1560.
6. Farooqi IS, Volders K, Stanhope R, Heuschkel R, White A, et al. (2007) Hyperphagia and early-onset obesity due to a novel homozygous missense mutation in prohormone convertase 1/3. J Clin Endocrinol Metab 9: 3369-3373.
7. Bell CG, Benzinou M, Siddiq A, Lecoeur C, Dina C, et al. (2004) Genome-wide linkage analysis for severe obesity in french caucasians finds significant susceptibility locus on chromosome 19q. Diabetes 7 pp. 1857-1865.
8. Benzinou M, Creemers JW, Choquet H, Lobbens S, Dina C, et al. (2008) Common nonsynonymous variants in pcsk1 confer risk of obesity. Nat Genet 8: 943-945.
9. Hager J, Dina C, Francke S, Dubois S, Houari M, et al. (1998) A genome-wide scan for human obesity genes reveals a major susceptibility locus on chromosome 10. Nat Genet 3: 304-308.
10. Renstrom F, Payne F, Nordstrom A, Brito EC, Rolandsson O, et al. (2009) Replication and extension of genome-wide association study results for obesity in 4923 adults from northern sweden. Hum Mol Genet 8: 1489-1496.
11. Kilpelainen TO, Bingham SA, Khaw KT, Wareham NJ, Loos RJ, (2009) Association of variants in the pcsk1 gene with obesity in the epic-norfolk study. Hum Mol Genet 18: 3496-3501.
12. Sandholt CH, Sparso T, Grarup N, Albrechtsen A, Almind K, et al. (2010) Combined analyses of 20 common obesity susceptibility variants. Diabetes 59: 1667-1673.
13. Heni M, Haupt A, Schäfer SA, Ketterer C, Thamer C, et al. (2010) Association of obesity risk SNPs in PCSK1 with insulin sensitivity and proinsulin conversion. BMC Med Genet Jun 9;11.
14. Jørgensen T, Borch-Johnsen K, Thomsen TF, Ibsen H, Glumer C, et al. (2003) A randomized non-pharmacological intervention study for prevention of ischaemic heart disease: Baseline results inter99. Eur J Cardiovasc Prev Rehabil 5: 377-386.
15. World Health Organization (1999) World Health Organization Diagnosis and Classification of Diabetes Mellitus: Report of a WHO Consultation. Part 1. Geneva, World Health Org.
16. Gjesing AP, Kjems LL, Vestmar MA, Grarup N, Linneberg A, et al. (2011) Carriers of the TCF7L2 rs7903146 TT genotype have elevated levels of plasma glucose, serum proinsulin and plasma gastric inhibitory polypeptide (GIP) during a meal test. Diabetologia 54 (1): 103-10.
17. Hansen T, Drivsholm T, Urhammer SA, Palacios RT, Vølund A, et al. (2007) The BIGTT test: a novel test for simultaneous measurement of pancreatic beta-cell function, insulin sensitivity, and glucose tolerance. Diabetes Care 2007 Feb;30 (2): 257-62.
18. DerSimonian R, Laird N, (1986) Meta-analysis in clinical trials. Elsevier ScienceInc. Science Direct 7: 177-188.
19. Nyholt DR, (2004) A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequlibrium with each other. Am J hum Genet 74: 765: 769.
20. Grarup N, Andersen G, Krarup NT, Albrechtsen A, Schmitz O, et al. (2008) Association Testing of Novel Type 2 Diabetes Risk Alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9 and NOTCH2 Loci With Insulin Release, Insulin Sensitivity, and Obesity in a Population-Based Sample of 4,516 Glucose-Tolerant Middle-Aged Danes. Diabetes 57: 2534-2540.
21. Meier JJ, Gallwitz B, Siepmann N, Holst JJ, Deacon CF, et al. (2003) Gastric inhibitory polypeptide (GIP) dose-dependently stimulates glucagon secretion in healthy human subjects at euglycaemia. Diabetologia 46: 798-801.
22. Irwin N, Flatt PR, (2009) Evidence for beneficial effects of compromised gastric inhibitory polypeptide action in obesity-related diabetes and possible therapeutic implications. Diabetologia 9: 1724-1731.
23. Lloyd DJ, Bohan S, Gekakis N, (2006) Obesity, hyperphagia and increased metabolic efficiency in pc1 mutant mice. Hum Mol Genet 11: 1884-1893.
24. O'Rahilly S, Gray H, Humphreys PJ, Krook A, Polonsky KS, et al. (1995) Brief report: Impaired processing of prohormones associated with abnormalities of glucose homeostasis and adrenal function. N Engl J Med 21: 1386-1390.