Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
BMC Medical Genetics
Published in: BMC Medical Genetics 1/2010

Open Access 01-12-2010 | Research article

A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population

Authors: Divya Sugunan, Anup K Nair, Harish Kumar, Anilkumar Gopalakrishnapillai

Published in: BMC Medical Genetics | Issue 1/2010

Login to get access

Abstract

Background

Glucose-dependent insulinotropic polypeptide (GIP) is one of the incretins, which plays a crucial role in the secretion of insulin upon food stimulus and in the regulation of postprandial glucose level. It also exerts an effect on the synthesis and secretion of lipoprotein lipase, from adipocytes, important for lipid metabolism. The aim of our study was to do a case-control association analysis of common variants in GIP in association with type 2 diabetes and related biochemical parameters.

Method

A total of 2000 subjects which includes 1000 (584M/416F) cases with type 2 diabetes and 1000 (470M/530F) normoglycemic control subjects belonging to Dravidian ethnicity from South India were recruited to assess the effect of single nucleotide polymorphisms (SNPs) in GIP (rs2291725, rs2291726, rs937301) on type 2 diabetes in a case-control manner. The SNPs were genotyped by using tetra primer amplification refractory mutation system-PCR (ARMS PCR). For statistical analysis, our study population was divided into sub-groups based on gender (male and female). Association analysis was carried out using chi-squared test and the comparison of biochemical parameters among the three genotypes were performed using analysis of covariance (ANCOVA).

Result

Initial analysis revealed that, out of the total three SNPs selected for the present study, two SNPs namely rs2291726 and rs937301 were in complete linkage disequilibrium (LD) with each other. Therefore, only two SNPs, rs2291725 and rs2291726, were genotyped for the association studies. No significant difference in the allele frequency and genotype distribution of any of the SNPs in GIP were observed between cases and controls (P > 0.05). Analysis of biochemical parameters among the three genotypes showed a significant association of total cholesterol (P = 0.042) and low density lipoprotein (LDL) with the G allele of the SNP rs2291726 in GIP (P = 0.004), but this was observed only in the case of female subjects. However this association does not remain significant after correction for multiple testing by Bonferroni's inequality method.

Conclusion

No statistically significant association was observed between any of the SNPs analysed and type 2 diabetes in our population. But the analysis of biochemical parameters indicates that the G allele in rs2291726 may be a putative risk allele for increased LDL cholesterol and further studies in other population needs to be carried out for ascertaining its role in cholesterol metabolism and subsequent cardiovascular risk.
Appendix
Available only for authorised users
Literature
1.
Prudente S, Morini E, Trischitta V: Insulin signaling regulating genes: effect on T2DM and cardiovascular risk. Nat Rev Endocrinol. 2009, 12: 682-693. 10.1038/nrendo.2009.215.CrossRef
2.
Unwin N, Whiting D, Gan D, Jacqmain O, Ghyoot G: International Diabetes Federation Diabetes Atlas. IDF Diabetes Atlas. 2009, International Diabetes Federation, Belgium, Fourth
3.
Ramachandran A, Snehalatha C, Viswanathan V, Viswanatha M, Haffner SM: Risk of non insulin dependent diabetes mellitus conferred by obesity and central adiposity in different ethnic groups: a comparative analysis between Asian Indians, Mexican Americans and Whites. DiabetesRes Clin Pract. 1997, 36: 121-125. 10.1016/S0168-8227(97)00040-5.CrossRef
4.
Radha V, Vimaleswaran KS, Babu HNS, Abate N, Chandalia M, Satija P, Grundy SM, Ghosh S, Majumder PP, Deepa R, Rao SMR, Mohan V: Role of genetic polymorphism peroxisome proliferator - Activated Receptor - 2 Pro 12Ala on ethnic susceptibility to diabetes in south Asian and caucasian subjects. (CURES-5). Diabetes Care. 2006, 29: 1046-1051. 10.2337/dc05-1473.CrossRefPubMed
5.
Vimaleswaran KS, Radha V, Ghosh S, Majumder PP, Deepa R, Babu HNS, Rao MRS, Mohan V: Peroxisome proliferators-activated receptor- co-activator -1 (PGC-1) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians (CURES-14). Diabetic Medicine. 2005, 22: 1516-1521. 10.1111/j.1464-5491.2005.01709.x.CrossRefPubMed
6.
Vimaleswaran KS, Radha V, Ramya K, Babu HNS, Savitha N, Roppa V, Monalisa D, Deepa R, Ghosh S, Majumder PP, Rao MRS, Mohan V: A novel association of polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians. Human Genetics. 2008, 123: 599-605. 10.1007/s00439-008-0506-8.CrossRefPubMed
7.
Pratley RE, Weyer C: The role of impaired early insulin secretion in the pathogenesis of Type II diabetes mellitus. Diabetologia. 2001, 44: 929-945. 10.1007/s001250100580.CrossRefPubMed
8.
Nauck MA, Baller B, Meier JJ: Gastric inhibitory polypeptide and glucagon-like peptide-1 in the pathogenesis of type 2 diabetes. Diabetes. 2004, 53 (Suppl 3): S190-S196. 10.2337/diabetes.53.suppl_3.S190.CrossRefPubMed
9.
Takeda J, Seino Y, Tanaka K, Fukumoto H, Kayano T, Takahashi H, Mitani T, Kurono M, Suzuki T, Tobe T, Imuru H: Sequence of an intestinal cDNA encoding human gastric inhibitory polypeptide precursor. Proc Natl Acad Sci USA. 1987, 84 (20): 7005-7008. 10.1073/pnas.84.20.7005.CrossRefPubMedPubMedCentral
10.
Buchan AM, Polak JM, Capella C, Solcia E, Pearse AG: Electron immunochemical evidence for the K cell localization of gastric inhibitory polypeptide (GIP) in man. Histochemistry. 1978, 56: 37-44. 10.1007/BF00492251.CrossRefPubMed
11.
Mortensen K, Christensen LL, Holst JJ, Orskov C: GLP-1 and GIP are colocalized in a subset of endocrine cells in the small intestine. Regul Pept. 2003, 114: 189-196. 10.1016/S0167-0115(03)00125-3.CrossRefPubMed
12.
Dupre J, Ross SA, Watson D, Brown JC: Stimulation of insulin secretion by gastric inhibitory polypeptide in man. J Clin Endocrinol Metab. 1973, 37: 826-828. 10.1210/jcem-37-5-826.CrossRefPubMed
13.
Ehses JA, Lee SST, Pederson RA, McIntosh CHS: A new pathway for glucose-dependent insulinotropic polypeptide (GIP) receptor signaling--Evidence for the involvement of phospholipase A, in GIP-stimulated insulin secretion. J Biol Chem. 2001, 276: 23667-23673. 10.1074/jbc.M103023200.CrossRefPubMed
14.
Wheeler MB, Gelling RW, McIntosh CH, Georgiou J, Brown JC, Pederson RA: Functional expression of the rat pancreatic islet glucose- dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties. Endocrinology. 1995, 136: 4629-4639. 10.1210/en.136.10.4629.PubMed
15.
Trumper A, Trumper K, Trusheim H, Arnold R, Goke B, Horsch D: Glucose-Dependent Insulinotropic Polypeptide Is a Growth Factor for b (INS-1) Cells by Pleiotropic Signaling. Mol Endocrinol. 2001, 15: 1559-1570. 10.1210/me.15.9.1559.PubMed
16.
Beguin P, Nagashima K, Nishimura N, Gonoi T, Seino S: PKA mediated phosphorylation of the human K-ATP channel: separate roles of Kir6.2 and SUR1 subunit phosphorylation. EMBO J. 1999, 18: 4722-4732. 10.1093/emboj/18.17.4722.CrossRefPubMedPubMedCentral
17.
Ding WG, Gromada J: Protein kinase A-dependent stimulation of exocytosis in mouse pancreatic beta-cells by glucose-dependent insulinotropic polypeptide. Diabetes. 1997, 46: 615-621. 10.2337/diabetes.46.4.615.CrossRefPubMed
18.
McIntosh CH, Wheeler MB, Gelling RW, Brown JC, Pederson RA: GIPRs and signal-transduction mechanisms. Acta Physiol Scand. 1996, 157: 361-365. 10.1046/j.1365-201X.1996.44267000.x.CrossRefPubMed
19.
Ehses JA, Casilla VR, Doty T, Pospisilik JA, Demuth HU, Pederson RA, Winter KD, McIntosh CH: Glucose-dependent Insulinotropic Polypeptide (GIP) Promotes {beta}-(INS-1) cell survival via cyclic AMP-mediated caspase-3 inhibition and regulation of p38 MAP kinase. Endocrinology. 2003, 144: 4433-4445. 10.1210/en.2002-0068.CrossRefPubMed
20.
Eckel RH, Fujimoto WY, Brunzell JD: Gastric inhibitory polypeptide enhanced lipoprotein lipase activity in cultured preadipocytes. Diabetes. 1979, 28: 1141-1142. 10.2337/diabetes.28.12.1141.CrossRefPubMed
21.
Miyawaki K, Yamada Y, Ban N, Ihara Y, Tsukiyama K, Zhou H, Fujimoto S, Oku A, Tsuda K, Toyokuni S, Hiai H, Mizunoya W, Fushiki T, Holst JJ, Makino M, Tashita A, Kobara Y, Tsubamoto Y, Jinnouchi T, Jomori T: Inhibition of gastric inhibitory polypeptide signaling prevents obesity. Nat Med. 2002, 8: 738-742. 10.1038/nm727.CrossRefPubMed
22.
Creutzfeldt W, Ebert R, Willms B, Frerichs H, Brown JC: Gastric inhibitorypolypeptide (GIP) and insulin in obesity: increased response to stimulation and defective feedback control of serum levels. Diabetologia. 1978, 14: 15-24. 10.1007/BF00429703.CrossRefPubMed
23.
Flatt PR, Bailey CJ, Kwasowski P, Swanston-Flatt SK, Marks V: Abnormalities of GIP in spontaneous syndromes of obesity and diabetes in mice. Diabetes. 1983, 32: 433-435. 10.2337/diabetes.32.5.433.CrossRefPubMed
24.
Yamada Y, Miyawaki K, Tsukiyama K, Harada N, Yamada C, Seini Y: Pancreatic and extrapancreatic effects of gastric inhibitory polypeptide. Diabetes. 2006, 55 (Suppl 2): S86-S91. 10.2337/db06-S011.CrossRef
25.
Nauck MA, Stöckmann F, Ebert R, Creutzfeldt W: Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986, 29: 46-52. 10.1007/BF02427280.CrossRefPubMed
26.
Vilsbøll T, Krarup T, Deacon CF, Madsbad S, Holst JJ: Reduced postprandial concentrations of intact biologically active glucagon-like peptide 1 in type 2 diabetic patients. Diabetes. 2001, 50: 609-13. 10.2337/diabetes.50.3.609.CrossRefPubMed
27.
Nitz I, Fisher E, Weikert C, Burwinkel B, Li Y, Möhlig M, Boeing H, Schreiber S, Schrezenmeir J, Döring F: Association analyses of GIP and GIPR polymorphisms with traits of the metabolic syndrome. Mol Nutr Food Res. 2007, 51 (8): 1046-52. 10.1002/mnfr.200700048.CrossRefPubMed
28.
Diagnosis and classification of diabetes mellitus. Diabetes care. 2004, 27 (Suppl 1): S5-S10.
29.
Miller SA, Dykes DD, Polesky HF: A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic acids research. 1988, 16 (3): 1215-10.1093/nar/16.3.1215.CrossRefPubMedPubMedCentral
30.
Ye S, Dhillon S, Ke X, Collins AR, Day IN: An efficient procedure for genotyping single nucleotide polymorphisms. Nucleic Acids Research. 2001, 29: 10.1093/nar/29.17.e88. No. 17 e88
31.
McIntyre N, Holsworth DC, Turner DS: New interpretation of oral glucose tolerance. Lancet. 1964, 2: 20-21. 10.1016/S0140-6736(64)90011-X.CrossRefPubMed
32.
Elrick H, Stimmler L, Hlad CJ, Arai Y: Plasma insulin response to oral and intravenous glucose administration. J Clin Endocrinol Metab. 1964, 24: 1076-1082. 10.1210/jcem-24-10-1076.CrossRefPubMed
33.
Chiba-Falek O, Nichols M, Suchindran S, Guyton J, Ginsburg GS, Barrett-Connor E, McCarthy JJ: Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study. BMC Med Genet. 2010, 11: 9-10.1186/1471-2350-11-9.CrossRefPubMedPubMedCentral
34.
Bush TL, Fried LP, Barrett-Connor E: Cholesterol, lipoproteins, and coronary heart disease in women. Clin Chem. 1988, 34 (8B): B60-70.PubMed
35.
Isken F, Pfeiffer AF, Nogueiras R, Osterhoff MA, Ristow M, Thorens B, Tschöp MH, Weickert MO: Deficiency of Glucose-Dependent Insulinotropic Polypeptide (GIP) receptor prevents ovariectomy-induced obesity in mice. Am J Physiol Endocrinol Metab. 2008, 295 (2): E350-355. 10.1152/ajpendo.00008.2008.CrossRefPubMedPubMedCentral
36.
Musso G, Gambino R, Pacini G, De Michieli F, Cassader M: Prolonged saturated fat-induced, glucose-dependent Insulinotropic polypeptide elevation is associated with adipokine imbalance and liver injury in nonalcoholic steatohepatitis: dysregulated enteroadipocyte axis as a novel feature of fatty liver. Am J Clin Nutr. 2009, 89: 558-567. 10.3945/ajcn.2008.26720.CrossRefPubMed
37.
Kim SJ, Nian C, McIntosh CH: Resistin is a key mediator of glucose dependent insulinotropic polypeptide (GIP) stimulation of lipoprotein lipase (LPL) activity in adipocytes. J Biol Chem. 2007, 282: 34139-34147. 10.1074/jbc.M704896200.CrossRefPubMed
38.
Meier JJ, Nauck MA, Kranz D, Holst JJ, Deacon CF, Gaeckler D, Schmidt WE, Gallwitz B: Secretion, Degradation, and Elimination of Glucagon-Like Peptide 1 and Gastric Inhibitory Polypeptide in Patients with Chronic Renal Insufficiency and Healthy Control Subjects. Diabetes. 2004, 53 (3): 654-662. 10.2337/diabetes.53.3.654.CrossRefPubMed
Metadata
Title
A case-control analysis of common variants in GIP with type 2 diabetes and related biochemical parameters in a South Indian population
Authors
Divya Sugunan
Anup K Nair
Harish Kumar
Anilkumar Gopalakrishnapillai
Publication date
01-12-2010
Publisher
BioMed Central
Published in
BMC Medical Genetics / Issue 1/2010
Electronic ISSN: 1471-2350
DOI
https://doi.org/10.1186/1471-2350-11-118

Other articles of this Issue 1/2010

BMC Medical Genetics 1/2010 Go to the issue

Correspondence

Practice guidelines for the molecular analysis of Prader-Willi and Angelman syndromes

Research article

Association of the apolipoprotein A5 gene -1131 T>C polymorphism with fasting blood lipids: a meta-analysis in 37859 subjects

Research article

MTNR1B rs10830963 is associated with fasting plasma glucose, HbA1Cand impaired beta-cell function in Chinese Hans from Shanghai

Research article

A gene-wide investigation on polymorphisms in the taste receptor 2R14 (TAS2R14) and susceptibility to colorectal cancer

Research article

Variant rs9939609 in the FTO gene is associated with body mass index among Chinese children

Research article

FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth