The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: Evidence for associations with type 2 diabetes and cholesterol levels

Lee, S. C.; Hashim, Y; Li, J. K. Y.; Ko, Gary T.C.; Critchley, J. A. J. H.; Cockram, Clive S.; Chan, Juliana C.N.

doi:10.1046/j.1365-2265.2001.01244.x

Cited by 53 publications

(57 citation statements)

References 25 publications

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“…S3 and Table S1), which agreed with the previous reports [16,17]. It is of interest to note that spectra showed modest differences in the region of 210-230 nm between the hIAPP and pIAPP fragments, where spectra of hIAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and hIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) showed more positive CD signals than those of pIAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29) and pIAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29) (Fig. 2A...…”

Section: Secondary Structures Determination By Far-uv CD and Spectra supporting

confidence: 89%

“…All decapeptides (IAPP (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)) and tridecapeptides (IAPP (17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)) were manually synthesized using standard 9-fluorenylmethyl chloroformate-based solid-phase peptide synthesis (SPPS) methodology as we previously described [8]. Crude peptides were purified by reverse phase high performance liquid chromatography using C4 semi-preparative or analytical column (Kromasil, AkzoNobel, Netherlands), and their identities were confirmed by ESI-MS.…”

Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

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Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

et al. 2010

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a b s t r a c tOf 10 variation sites between sequences of amyloid-resistant porcine islet amyloid polypeptide (pIAPP) and amyloid-prone human IAPP (hIAPP), seven locate within residues 17-29, the most amyloidogenic fragment within hIAPP. To investigate how these variations affect amyloidogenicity, 26 IAPP(17-29) or IAPP(20-29) variants were synthesized and their secondary structures, amyloidogenicity, oligomerization and cytotoxicity were studied. Our results indicated that pIAPP fragments are refractory to amyloid formation and significantly less cytotoxic compared with hIAPP fragments. A novel stable dimer was observed in pIAPP(20-29) solution, whereas hIAPP(20-29) exists mostly as monomers and trimers. Among all human to porcine substitutions, S20R caused the most prolonged lag time and significantly attenuated cytotoxicity. The different oligomerization and amyloidogenic properties of hIAPP and pIAPP fragments are discussed.

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Section: Secondary Structures Determination By Far-uv CD and Spectra supporting

confidence: 89%

Section: Peptide Synthesis and Purificationmentioning

confidence: 99%

Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

et al. 2010

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“…A missense heterozygous substitution in hIAPP at position 20 of a serine residue for a glycine has been identified in Japanese and Chinese studies [63]. However the prevalence of the mutation in T2DM is low, although significant, in both Japanese (2.6% in T2DM vs 0.8% in non-diabetic group, p<0.0007) [64] and Chinese cohorts (2.0-2.8% in T2DM; 0-0.5% in controls, p<0.05) [65] but not found in large cohorts of Caucasians [66]. The S20G mutation is associated with only moderate alterations in insulin secretion in the small number of patients examined so far and, therefore, its role in T2DM is unclear [67].…”

Section: Genetically Determined Structural Changesmutations In the Iamentioning

confidence: 99%

Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?

2004

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The role of islet amyloidosis in the onset and progression of Type 2 diabetes remains obscure. Islet amyloid polypeptide is a 37 amino-acid, beta-cell peptide which is co-stored and co-released with insulin. Human islet amyloid polypeptide refolds to a β-conformation and oligomerises to form insoluble fibrils; proline substitutions in rodent islet amyloid polypeptide prevent this molecular transition. Pro-islet amyloid polypeptide (67 amino acids in man) is processed in secretory granules. Refolding of islet amyloid polypeptide may be prevented by intragranular heterodimer formation with insulin (but not proinsulin). Diabetes-associated abnormal proinsulin processing could contribute to de-stabilisation of granular islet amyloid polypeptide. Increased pro-islet amyloid polypeptide secretion as a consequence of islet dysfunction could promote fibrillogenesis; the propeptide forms fibrils and binds to basement membrane glycosamino-glycans. Islet amyloid polypeptide gene polymorphisms are not universally associated with Type 2 diabetes. Transgenic mice expressing human islet amyloid polypeptide gene have increased islet amyloid polypeptide concentrations but develop islet amyloid only against a background of obesity and/or high fat diet. In transgenic mice, obese monkeys and cats, initially small perivascular deposits progressively increase to occupy 80% islet mass; the severity of amyloidosis in animal models is related to the onset of hyperglycaemia, suggesting that islet amyloid and the associated destruction of islet cells cause diabetes. In human diabetes, islet amyloid can affect less than 1% or up to 80% of islets indicating that islet amyloidosis largely results from diabetes-related pathologies and is not an aetiological factor for hyperglycaemia. However, the associated progressive betacell destruction leads to severe islet dysfunction and insulin requirement. [Diabetologia (2004) 47:157-169]

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“…The amylin gene coding region mutation, S20G, reported in Japanese and Chinese populations [9,10], was not observed in Maori patients or control subjects and is therefore not likely to be a major contributing factor for Type 2 diabetes in Maori people despite evidence for a common genetic origin for these populations [7,8].…”

Section: Resultsmentioning

confidence: 99%

“…A missense mutation in the amylin gene, S20G, has been shown to predispose Japanese and Chinese [9,10], but not Caucasian populations [11,12] to Type 2 diabetes. This mutation was prevalent in 0.4% of Chinese and 4.1% of Japanese patients with late-onset Type 2 diabetes.…”

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confidence: 99%

Amylin gene promoter mutations predispose to Type 2 diabetes in New Zealand Maori

2003

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Aims/hypothesis. Amylin gene mutations are known to predispose Chinese and Japanese subjects, but not Caucasian subjects, to Type 2 diabetes. New Zealand Maori, who have a high prevalence of Type 2 diabetes, have genetic origins in South East Asia. Amylin gene mutations could therefore predispose New Zealand Maori to Type 2 diabetes. Methods. The amylin gene was screened for mutations in the proximal promoter region, exons 1 and 2, intron 1, and coding region of exon 3 by polymerase chain reaction amplification and direct sequencing of 131 Type 2 diabetic Maori patients and 258 non-diabetic Maori control subjects. Results. We identified three new amylin gene mutations: two mutations in the promoter region (-215T>G and −132G>A) and a missense mutation in exon 3 (Q10R). The −215T>G mutation was observed in 5.4% of Type 2 Maori diabetic patients and predisposed the carrier to diabetes with a relative risk of 7.23. The −215T>G mutation was inherited with a previously described amylin promoter polymorphism (−230A>C) in 3% of the Maori with Type 2 diabetes, which suggests linkage disequilibrium exists between these two mutations. The −230A>C polymorphism on its own, however, was not associated with Type 2 diabetes in Maori subjects. The −132G>A and Q10R mutations were both observed in 0.76% of Type 2 diabetic patients and were absent in non-diabetic subjects. Conclusion/Interpretation. The amylin gene mutations identified in this study are associated with Type 2 diabetes in 7% of Maori. Amylin is likely to be an important susceptibility gene for Type 2 diabetes in Maori people. [Diabetologia (2003) 46:574-578]

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The islet amyloid polypeptide (amylin) gene S20G mutation in Chinese subjects: Evidence for associations with type 2 diabetes and cholesterol levels

Abstract: Our data suggest that the islet amyloid polypeptide gene mutation might be associated with early occurrence of type 2 diabetes and lower plasma levels of total and low density lipoprotein-cholesterol in the Chinese population.

Cited by 53 publications

References 25 publications

Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

Porcine islet amyloid polypeptide fragments are refractory to amyloid formation

Islet amyloid: a complication of islet dysfunction or an aetiological factor in Type 2 diabetes?

Amylin gene promoter mutations predispose to Type 2 diabetes in New Zealand Maori

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