ASSOCIATION OF GLUTATHIONE-S-TRANSFERASE
(GSTM1 and GSTT1) AND FTO GENE POLYMORPHISMS
WITH TYPE 2 DIABETES MELLITUS CASES
IN NORTHERN INDIA
Raza ST, Abbas S, Ahmad A, Ahmed F, Zaidi ZH, Mahdi F
*Corresponding Author: Syed Tasleem Raza, Ph.D., Molecular Biology Laboratory, Department of Biochemistry,
Era’s Lucknow Medical College and Hospital, Hardoi Road, Lucknow, Uttar Pradesh, India 226025. Tel.: +91-522-
240-8122; 240-8123. Fax: +91-522-240-7824. E-mail: tasleem24@gmail.com
page: 47
|
|
DISCUSSION
GSTM1 and GSTT1 Gene Polymorphisms.
Type 2 diabetes mellitus is characterized as being a
polygenic disorder and generally thought of as a syndrome,
rather than a single specific entity. Oxidative
stress plays a major role in the pathogenesis of T2DM
[23]. Glutathione-S-transferases catalyze the conjugation
of glutathione to a wide range of electrophiles
and represent a protective mechanism against oxidative
stress. The GST family of genes is critical in the
protection of cells from ROS because they utilize as
substrates a wide variety of products of oxidative
stress [24]. The deletion polymorphisms of GSTT1
and GSTM1, which are associated with abolished enzyme
activity [25], have been associated with T2DM
when compared to control subjects [9,24]. The majority
of case control studies of GSTM1 and GSTT1
null genotypes have reported risk associations with
disease [26,27].The frequency of the GSTM1 null
genotype in our study was 38.61%; it is little lower
than reported in other populations (Egyptian 58.62%,
Dubai 57.5%, North Indian 54.00%) [28-30]. The
frequency of the GSTTI null genotype was 7.92% in
T2DM patients, which is lower when compared to
the Dubai (60.0%) and Egyptian (35.0%) populations
[7,29]. We have also observed that the genotype
frequency of the positive GSTT1 and GSTM1 genes
was 92.07 and 61.38%, respectively, which is significantly
higher in comparison with Dubai where the
positive GSTT1 and GSTM1 genes was 40.0 and
42.5%, respectively [29].
The FTO Gene Polymorphism. The frequency
of the FTO gene polymorphism is quite variable
in different geographic and ethnic groups (Table 3).
Previous studies have shown that T2DM risk associated
with the A allele of the FTO variant (rs
9939609) was strongly mediated by BMI, and has
been shown to potentially affect mass rather than
height [31]. The FTO gene (rs 9939609) was shown
to be strongly associated with T2DM risk (OR 1.27;
p = 5 × 10-8) in a genome wide association (GWA)
scan performed in the UK population [31]. In our study, we reported that the frequency of the AT genotype
(Pro12Ala) was 71.29% in T2DM patients,
which is significantly higher when compared with
North Indians (47.6%), South Asian Indians
(42.2%), South Africans (55.0%), Scots (48.8%)
and Spanish (48.3%) populations [32-36]. The frequency
of the FTO AA genotype described in other
populations fluctuates between 14.0 to 18.0% in
T2DM patients of North Indians (12.5%), South
Asian Indians (14.2%), Scots (18.0%) and Spanish
(17.8%) populations [32,33,35,36], but the frequency
of the FTO AA genotype in our study group was
4.95%, which is considerably lower when compared
to other reports. Many factors may account for the
different results in similar studies. In our population,
the frequency of the TT genotype was 23.76%,
which is considerably lower than in South Asian Indians
(43.6%) and North Indians (39.9%) [32,33],
There may be differences even in the same population
because of genetic, environmental factors and
the number of samples analyzed.
Our data suggest that the polymorphism in the
GSTM1 gene might be a risk factor for T2DM, while
no significant association was found with the FTO
gene polymorphism. The potential role of GST and
FTO gene polymorphisms as a marker of susceptibility
for T2DM needs further studies in a larger
number of patients.
Declaration of Interest. We are grateful for the
support of the intramural grant from the Era’s Lucknow
Medical College and Hospital, Lucknow, Uttar
Pradesh, India. The authors report no conflicts of
interest. The authors alone are responsible for the
content and writing of this article.
|
|
|
|
 |
Number 27
VOL. 27 (2), 2024 |
Number 27
VOL. 27 (1), 2024 |
Number 26
Number 26 VOL. 26(2), 2023 All in one |
Number 26
VOL. 26(2), 2023 |
Number 26
VOL. 26, 2023 Supplement |
Number 26
VOL. 26(1), 2023 |
Number 25
VOL. 25(2), 2022 |
Number 25
VOL. 25 (1), 2022 |
Number 24
VOL. 24(2), 2021 |
Number 24
VOL. 24(1), 2021 |
Number 23
VOL. 23(2), 2020 |
Number 22
VOL. 22(2), 2019 |
Number 22
VOL. 22(1), 2019 |
Number 22
VOL. 22, 2019 Supplement |
Number 21
VOL. 21(2), 2018 |
Number 21
VOL. 21 (1), 2018 |
Number 21
VOL. 21, 2018 Supplement |
Number 20
VOL. 20 (2), 2017 |
Number 20
VOL. 20 (1), 2017 |
Number 19
VOL. 19 (2), 2016 |
Number 19
VOL. 19 (1), 2016 |
Number 18
VOL. 18 (2), 2015 |
Number 18
VOL. 18 (1), 2015 |
Number 17
VOL. 17 (2), 2014 |
Number 17
VOL. 17 (1), 2014 |
Number 16
VOL. 16 (2), 2013 |
Number 16
VOL. 16 (1), 2013 |
Number 15
VOL. 15 (2), 2012 |
Number 15
VOL. 15, 2012 Supplement |
Number 15
Vol. 15 (1), 2012 |
Number 14
14 - Vol. 14 (2), 2011 |
Number 14
The 9th Balkan Congress of Medical Genetics |
Number 14
14 - Vol. 14 (1), 2011 |
Number 13
Vol. 13 (2), 2010 |
Number 13
Vol.13 (1), 2010 |
Number 12
Vol.12 (2), 2009 |
Number 12
Vol.12 (1), 2009 |
Number 11
Vol.11 (2),2008 |
Number 11
Vol.11 (1),2008 |
Number 10
Vol.10 (2), 2007 |
Number 10
10 (1),2007 |
Number 9
1&2, 2006 |
Number 9
3&4, 2006 |
Number 8
1&2, 2005 |
Number 8
3&4, 2004 |
Number 7
1&2, 2004 |
Number 6
3&4, 2003 |
Number 6
1&2, 2003 |
Number 5
3&4, 2002 |
Number 5
1&2, 2002 |
Number 4
Vol.3 (4), 2000 |
Number 4
Vol.2 (4), 1999 |
Number 4
Vol.1 (4), 1998 |
Number 4
3&4, 2001 |
Number 4
1&2, 2001 |
Number 3
Vol.3 (3), 2000 |
Number 3
Vol.2 (3), 1999 |
Number 3
Vol.1 (3), 1998 |
Number 2
Vol.3(2), 2000 |
Number 2
Vol.1 (2), 1998 |
Number 2
Vol.2 (2), 1999 |
Number 1
Vol.3 (1), 2000 |
Number 1
Vol.2 (1), 1999 |
Number 1
Vol.1 (1), 1998 |
|
|
