Analysis of Metallothionein Gene MT1A (rs11076161) and MT2A (rs10636) Polymorphisms as a Molecular Marker in Type 2 Diabetes Mellitus among Malay Population

Type 2 diabetes mellitus (T2DM) is a complex
metabolic disorder that characterized by the presence of high glucose
in blood that cause from insulin resistance and insufficiency due to
deterioration β-cell Langerhans functions. T2DM is commonly
caused by the combination of inherited genetic variations as well as
our own lifestyle. Metallothionein (MT) is a known cysteine-rich
protein responsible in helping zinc homeostasis which is important in
insulin signaling and secretion as well as protection our body from
reactive oxygen species (ROS). MT scavenged ROS and free
radicals in our body happen to be one of the reasons of T2DM and its
complications. The objective of this study was to investigate the
association of MT1A and MT2A polymorphisms between T2DM and
control subjects among Malay populations. This study involved 150
T2DM and 120 Healthy individuals of Malay ethnic with mixed
genders. The genomic DNA was extracted from buccal cells and
amplified for MT1A and MT2A loci; the 347bp and 238bp banding
patterns were respectively produced by mean of the Polymerase
Chain Reaction (PCR). The PCR products were digested with Mlucl
and Tsp451 restriction enzymes respectively and producing
fragments lengths of (158/189/347bp) and (103/135/238bp)
respectively. The ANOVA test was conducted and it shown that there
was a significant difference between diabetic and control subjects for
age, BMI, WHR, SBP, FPG, HBA1C, LDL, TG, TC and family
history with (P<0.05). While the HDL, CVD risk ratio and DBP does
not show any significant difference with (P>0.05). The genotype
frequency for AA, AG and GG of MT1A polymorphisms was 72.7%,
22.7% and 4.7% in cases and 15%, 55% and 30% in control
respectively. As for MT2A, genotype frequency of GG, GC and CC
was 42.7%, 27.3% and 30% in case and 5%, 40% and 55% for
control respectively. Both polymorphisms show significant difference
between two investigated groups with (P=0.000). The Post hoc test
was conducted and shows a significant difference between the
genotypes within each polymorphism (P=0. 000). The MT1A and
MT2A polymorphisms were believed to be the reliable molecular
markers to distinguish the T2DM subjects from healthy individuals in
Malay populations.





References:
<p>[1] Arora, N., &amp; Chertow, G. M. (2011). Update in nephrology: evidence
published in 2010. Annals of internal medicine, 154(12), 824-829.
[2] Cai, L. (2004). Metallothionein as an adaptive protein prevents diabetes
and its toxicity. Nonlinearity in Biology, Toxicology, and Medicine, 2(2),
89-103.
[3] Chen, H., Carlson, E. C., Pellet, L., Moritz, J. T., &amp; Epstein, P. N.
(2001). Overexpression of metallothionein in pancreatic &beta;-cells reduces
streptozotocin-induced DNA damage and diabetes. Diabetes, 50(9),
2040-2046.
[4] Chen, X., Lei, L., Tian, L., Zhu, G., &amp; Jin, T. (2012). Bone mineral
density and polymorphisms in metallothionein 1A and 2A in a Chinese
population exposed to cadmium. Science of the Total Environment, 423,
12-17.
[5] Cipriano, C., Malavolta, M., Costarelli, L., Giacconi, R., Muti, E.,
Gasparini, N., ... &amp; Mocchegiani, E. (2006). Polymorphisms in MT1a
gene coding region are associated with longevity in Italian Central
female population. Biogerontology,7(5-6), 357-365.
[6] Ganasyam, S. R., Rao, T. B., Murthy, Y. S. R., Jyothy, A., &amp; Sujatha,
M. (2012). Association of Estrogen Receptor-&alpha; Gene &amp; Metallothionein-
1 Gene Polymorphisms in Type 2 Diabetic Women of Andhra
Pradesh. Indian Journal of Clinical Biochemistry, 27(1), 69-73.
[7] Letchuman, G. R., Wan Nazaimoon, W. M., Wan Mohamad, W. B.,
Chandran, L. R., Tee, G. H., Jamaiyah, H., ... &amp; Ahmad Faudzi, Y.
(2010). Prevalence of diabetes in the Malaysian national health
morbidity survey III 2006. Med J Malaysia, 65(3), 180-186.
[8] Riaz, S., Alam, S. S., Srai, S. K., Skinner, V., Riaz, A., &amp; Akhtar, M. W.
(2010). Proteomic identification of human urinary biomarkers in
diabetes mellitus type 2. Diabetes technology &amp; therapeutics, 12(12),
979-988.
[9] Saltiel, A. R. (2001). New perspectives into the molecular pathogenesis
and treatment of type 2 diabetes. Cell, 104(4), 517.
[10] Skutkova, H., Babula, P., Stiborova, M., Eckschlager, T., Trnkova, L.,
Provaznik, I., ... &amp; Adam, V. (2012). Structure, Polymorphisms and
Electrochemistry of Mammalian Metallothioneins&ndash;A Review. Int. J.
Electrochem. Sci, 7, 12415-12431.
[11] Van-Tilburg, J., Van Haeften, T. W., Pearson, P., &amp; Wijmenga, C.
(2001). Defining the genetic contribution of type 2 diabetes
mellitus. Journal of medical genetics, 38(9), 569-578.
[12] Wild, S. H., Roglic, G., Green, A., Sicree, R., &amp; King, H. (2004). Global
Prevalence of Diabetes: Estimates for the Year 2000 and Projections for
2030 Response to Rathman and Giani. Diabetes care, 27(10), 2569-
2569.
[13] Yang, L., Li, H., Yu, T., Zhao, H., Cherian, M. G., Cai, L., &amp; Liu, Y.
(2008). Polymorphisms in metallothionein-1 and-2 genes associated with
the risk of type 2 diabetes mellitus and its complications. American
Journal of Physiology-Endocrinology And Metabolism, 294(5), E987-
E992.</p>