OAR@UM Collection:https://www.um.edu.mt/library/oar/handle/123456789/642002026-04-27T05:23:02Z2026-04-27T05:23:02ZMolecular SNPlotypes™ with common alleles reflects expression profile in Diabetes Mellitus Type 2https://www.um.edu.mt/library/oar/handle/123456789/316322020-11-19T13:54:20Z2008-01-01T00:00:00ZTitle: Molecular SNPlotypes™ with common alleles reflects expression profile in Diabetes Mellitus Type 2
Abstract: Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder and is one of the cardiovascular risk
factors cumulatively giving rise to a metabolic syndrome (MS). The pathophysiology of
T2DM is related to underplaying multiple genes. In this study 20 Single Nucleotide
Polymorphisms (SNPs) panel I, associated with T2DM were characterised after PCR and
RFLP using DNA samples from Maltese and Libyan T2DM patients, and their respective
reference populations. 7/20 cognate SNPs (panel II) at different loci representing different
genes (ADRAB~2 [nt46 A-7G], FABP2 [codon 54 G-7A], UCPl [nt3826 A-7G], LEPTIN
[nt -2549 C-7A], IPFl [codon 18 T-7C], IL-6 [-174 G-7C], TCF7L2 [IVS3 T-7G]) showed
significance association with T2DM having a significant odds ratio of 1.7 to 4.2. These genes
represent inflammatory response genes, metabolic syndrome genes and MODY genes. An
innovative concept of SNPlotyping TM has revealed the impact of the number of mutant alleles
resulting in a SNPlotypingTM score that enhances the association with T2DM patients in the 2
populations. The distribution of SNPs in the different SNPlotypesTM indicates that ~2
adrenergic receptor is highly represented (44%) followed by FABP2 (44%), TCF7L2 (41 %),
Leptin (35%), IL6 (27%) and UCPl (24%). The SNPlotype with the highest association in
the population study was found to be significant and inherited together with the disorder in a
family study.
Another part of this study the response to drugs (Insulin, Metformin and Glibenclamide) by
the selected Maltese T2DM patients representing the different SNPlotypes was measured as a
function of differential expression of a gene using RT-PCR on mRNA extracted from
monocyte of Maltese T2DM patients. Only ~2 adrenergic receptor (ADRAB~2) transcripts
were detected in the untreated and treated monocytes. The differential expression of
ADRAB~2 indicates that there is a relation between the response to the drug and the
SNPlotype of the patient. Interestingly, the expression of ADRAB~2 was downregulated in
response to Insulin and Metformin in patients with SNPlotypes lacking the ADRAB~2
mutation, while the expression was upregulated in the other SNPlotypes. The outcome of
ADRAB~2 mRNA transcript was dependent on patient SNPlotypeTM, when ranked by
wildtype and mutant UCPl and ADRAB~2 polymorphisms.
In conclusion some metabolic and inflammatory alleles where characterized in the Maltese
and Libyan populations. SNPlotypeTM enhances the association to measure the risk for a
particular disorder and we give evidence that it can be used to classify patients into potentially
therapeutic groups.
Description: PH.D.2008-01-01T00:00:00Z