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Molecular Characterization of Insulin Gene in Diabetic Foot Ulcer Patients: A Pilot Study from Bengal Bay Coastal Origin
Objective: Many studies have showed that foot ulcer is the most frequent occurrence among diabetic patients in the south Indian origin. This study aimed to investigate on the hypothesis that in patients with diabetic foot ulcer in south Indian subjects there is a substitution within nucleotide sequence of coding region related to insulin gene and this may be signifying a link disequilibrium with the class III allele in the insulin gene locus, which can be considered due to its relevance with diabetes. We aim to examine this part of insulin gene to find out if there is any mutation within the insulin gene sequence that is relevant with diabetes mellitus. Materials and Methods: We used the PCR products of the amplified insulin gene from 40 patients diagnosed with foot ulcer seeking mutations, which might be in association with the class III allele and therefore indicates its relevance with the manifestation of diabetic foot ulcers. Results: We identified a β-chain mutant (i.e. insulin Chicago) using the restriction enzyme (MboII) in individuals afflicted with foot ulcer. A couple of patterns (α and β) were found indicating the presence of PstI polymorphism within the 3' un-translated part of the insulin gene. Besides, allele frequencies in subjects homozygous for α allele, homozygous for β allele and heterozygous were respectively 0.3 (12/40), 0.125 (5/40) and 0.575 (23/40). No significant variant regarding allelic frequency was characterized between the patients and normal controls, though a mutation in B-chain (insulin Chicago) was observed. Conclusion: Despite linkage disequilibrium between this polymorphism in the 3' un-translated portion of the insulin gene and the class III allele, it is unlikely to have advantage than the class III allele itself on prognosticating diabetes.
Diabetes mellitus, Insulin Gene, Polymerase Chain Reaction.
- Teo AK, Wagers AJ, Kulkarni RN. New opportunities: harnessing induced pluripotency for discovery in diabetes and metabolism. Cell Metabolism. 2013; 18(6):775–91.
- Chakravarti A, Elbein SC, Permutt MA. Evidence for increased recombination near the human insulin gene: implication for disease association studies. Proceedings of the National Academy of Sciences.1986; 83(4):1045–9.
- Avagian A. Education program for non-insulin-dependent (type 2) diabetes mellitus patients, aged 40-45, in Yerevan and evaluation of the program (Doctoral dissertation, American University of Armenia (AUA)).
- Allen MD, Doherty TJ, Rice CL, Kimpinski K. Physiology in Medicine: Neuromuscular consequences of diabetic neuropathy.Journal of Applied Physiology. 2016; 121(1):1–6.
- Omar MA, Hammond MG, Motala AA, Seedat MA.HLA class I and II antigens in South African Indians with NIDDM. Diabetes. 1988; 37(6):796–9.
- Hinchliffe RJ, Brownrigg JR, Apelqvist J, Boyko EJ, Fitridge R, Mills JL, Reekers J, Shearman CP, Zierler RE, Schaper NC. IWGDF guidance on the diagnosis, prognosis and management of peripheral artery disease in patients with foot ulcers in diabetes. Diabetes/Metabolism Research and Reviews. 2016; 32(S1):37–44.
- Arya M, Shergill IS, Williamson M, Gommersall L, Arya N, Patel HR. Basic principles of real-time quantitative PCR.Expert Review of Molecular Diagnostics. 2005; 5(2):209– 19.
- Bell GI, Pictet RL, Rutter WJ, Cordell B, Tischer E, Goodman HM. Sequence of the human insulin gene. Nature.1980; 284(5751):26–32.
- Quinn TW, White BN. Analysis of DNA sequence variation.Avian Genetics: A Population and Ecological Approach.1987; 163–98.
- Hitman GA, Jowett NI, Williams LG, Humphries S, Winter RM, Galton DJ. Polymorphisms in the 5’-flanking region of the insulin gene and non-insulin-dependent diabetes. Clinical science (London, England: 1979). 1984; 66(4):383–8.
- Winter WE, Signorino MR. Diabetes mellitus: pathophysiology, etiologies, complications, management, and laboratory evaluation: special topics in diagnostic testing. Amer Assoc for Clinical Chemistry. 2002.
- Kambo PK, Hitman GA, Mohan V, Ramachandran A, Snehalatha C, Suresh S, Metcalfe K, Ryait BK, Viswanathan M.The genetic predisposition to fibrocalculous pancreatic diabetes.Diabetologia. 1989; 32(1):45–51.
- Takeda J, Seinoz Y, Yoshimasa Y, Fukumoto H, Kohl G, Kuzuya H, Imura H, Seino S. Restriction fragment length polymorphism (RFLP) of the human insulin receptor gene in Japanese: its possible usefulness as a genetic marker. Diabetologia.1986; 29(9):667–9.
- Lahiri DK, Nurnberger Jr JI. A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Research. 1991; 19(19):5444.
- Elbein SC, Corsetti L, Permutt MA. New polymorphisms at the insulin locus increase its usefulness as a genetic marker.Diabetes. 1985; 34(11):1139–44.
- Elbein SC. Molecular and clinical characterization of an insertional polymorphism of the insulin-receptor gene. Diabetes.1989; 38(6):737–43.
- Elbein SC, Borecki I, Corsetti L, Fajans SS, Hansen AT, Nerup J, Province M, Permutt MA. Linkage analysis of the human insulin receptor gene and maturity onset diabetes of the young. Diabetologia. 1987; 30(8):641–7.
- Hitman GA, Kambo PK, Viswanathan M, Mohan V. An analysis of amplified insulin gene products in diabet ics of Indian origin. Journal of Medical Genetics.1991; 28(2):97–100.
- Li SR, Oelbaum RS, Baroni MG, Stock J, Galton DJ. Association of genetic variant of the glucose transporter with non-insulin-dependent diabetes mellitus. The Lancet.1988; 332(8607):368–70.
- Kwok SC, Steiner DF, Rubenstein AH, Tager HS. Identification of a point mutation in the human insulin gene giving rise to a structurally abnormal insulin (insulin Chicago). Diabetes. 1983; 32(9):872–5.
- Islam MA, Bhayye S, Adeniyi AA, Soliman ME, Pillay TS.Diabetes mellitus caused by mutations in human insulin: analysis of impaired receptor binding of insulins Wakayama, Los Angeles and Chicago using pharmacoinformatics.Journal of Biomolecular Structure and Dynamics. 2016; 14:1–4
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