Oxidative stress has been considered to be a common pathogenic factor in diabetes and its complications [21
]. The family of GST genes plays an important role in protecting cells from oxidative stress. GSTP1 catalyses the detoxification of products arising from DNA oxidation [22
]. A defect in detoxifying reactive oxygen species, which is genetically determined, may influence the development and severity of diabetes mellitus [16
There are many studies dealing with GSTP1 polymorphism in various diseases, but only a few studies have addressed the role of GSTP1 gene polymorphism in diabetes. Therefore, the current study was designed to investigate the role of GST-P1 (Ile105Val) gene polymorphism in T2DM patients and healthy controls and whether this variant modulates the glycemic control in Egyptian patients with T2DM.
Our results demonstrate that the frequency of the G allele was higher in the diabetics compared to controls (OR = 1.69, 95% CI = 1.024-2.78, p = 0.03). Additionally, significant differences in the frequencies of the Ile/Val genotype between patients and the control group were observed (30.4% vs. 19.2% respectively). We therefore suggest that the G allele (Val) of GSTP1 Ile105Val plays an important role in predisposition to T2DM.
There have been controversial results regarding the association between GSTP1 Ile105
Val gene polymorphism and diabetes development. We are in agreement with Ramprasath et al
] and Bid et al
], who demonstrated that the GSTP1 G allele (Val) and its variant genotype (Il/Val) play a vital role in the development of diabetes mellitus. In contrast, Yalin et al
] and Oniki et al
] suggested that GSTP1 Ile105
Val polymorphism may not play a significant role in the etiopathogeneses of DM in the Turkish population and Japanese population respectively. These inconsistent data could be explained by ethnic differences in the selected study groups [25
To investigate the association between GSTP1 Ile105Val gene polymorphism and glycemic control in relation to T2DM we evaluated HbA1c and serum glucose levels in different genotypes. No association between the gene polymorphism and glycemic control parameters in T2DM patients was detected. To our knowledge, this study is the first attempt to evaluate the effect of the GSTP1 genotypes with regard to glycemic control parameters in T2DM.
The epidemic of T2DM observed in recent years is a clear indication of the importance of environmental factors in diabetes onset, in particular obesity and physical inactivity [23
]. Obesity, mainly when fat is distributed predominantly at the abdominal level, is the main risk factor for T2DM. Our study is probably the first study to show that GSTP1 heterozygosity (Ile/Val) is significantly associated with BMI.
Dyslipidemia observed in T2DM is one of the major factors contributing to vascular risk [26
]. In the current study, we further investigated the effect of the genotypes on the lipid profile. There was no association between the genotypes and lipid profile in diabetic patients. This data are consistent with the previous reports which demonstrated that there was no association between GSTP1 genotypes and blood lipids in T2DM patients [15
GSTP1 detoxifies cigarette smoke-derived toxins and endogenously derived reactive oxygen species. Therefore, it is conceivable that genetic polymorphism in GSTP1 may have an effect on smoking-related risk in T2DM. Concerning the relation to smoking status, previous report showed that active smoking is associated with an increased risk of T2DM [27
]. We found that GSTP1 polymorphism was not significantly linked with smoking in T2DM patients. These data are in accordance with Oniki et al
In conclusion, this is the first study to determine the association of type 2 diabetes with GSTP1 Ile105Val gene polymorphism in the Egyptian population and its effect on glycemic control parameters. These results show that GSTP1 Ile/Val genotype may play a significant role in the etiopathogeneses of T2DM, and the GSTP1 gene may be a useful marker in the prediction of T2DM susceptibility of the Egyptian population regardless of smoking status. Our findings suggest that the GSTP1 gene polymorphism had no apparent effect on glycemic control in type 2 diabetes patients; meanwhile, there was a significant correlation with BMI in diabetics. Although some of our data were statistically significant, we acknowledge that the findings presented here are preliminary because of the small number of subjects and that the study requires confirmation in a separate, larger cohort. Additionally, a wide epidemiological study is needed to test the possible association between genotypic and phenotypic effects of other GST gene polymorphisms in diabetic patients.