Susceptibility to T1D is determined by complex interactions between several genetic loci and environmental factors. Many of them harbor functional candidates likely involved in autoimmunity and potentially in T1D pathogenesis, and relevant examples are PTPN22 and IL2RA genes [9,10,11].
In our study, we found a statistically significant difference between patient and control groups regarding family history (p < 0.001). This finding was in agreement with Pociot et al.  who reported that the risk to develop T1D increases to1 in 20 in a population who have the first-degree relative with T1DM, while the risk among the general population is 1 in 300.
In our study, the distribution of PTPN22 (C1858T) polymorphisms revealed that the distribution of the homozygous pattern (TT) was a 5% in patient group versus 0% in the control group, while heterozygous pattern (TC) was 84% inpatient group versus 60% in the control group. On the other hand, wild variant (CC) was 11% in patient group versus 40% in the control group, all these results of genotypic variation showed a statistically significant difference between patients and controls (p = 0.028). These findings were obvious while analyzing the allelic distribution of high frequency of T allele that was of statistical significance between the studied groups.
Our genotypic results were in agreement with Bottini et al. , who firstly reported an association between the PTPN22 polymorphism and T1D from North America and Sardinia. On the frame of the necessity of throughout additional research to clarify the varied geographic distribution, recent several studies involved different populations had explored the relationship between PTPN22 and T1M including those from Italy [14, 15], Spain , Denmark , Finland , Brazil , France , Germany [21, 22], the UK , Poland , Greece , China , and Egypt . On the contrary, other studies were reported which denied the association between 1858C/T polymorphism and susceptibility to T1D [28, 29].
These contradictory results can be explained by the limited size of the sample, genetic heterogeneity among the studied populations, the different environmental factors involved in the pathogenesis of T1D, or other methodological issues.
Regarding the association between gender, age of onset of T1D, type of presentation, and PTPN22 C1858T in T1D patients, in our study, there was statistically insignificant difference between PTPN22 genotypes (TT, TC, and CC) and the above mentioned parameters (P > 0.05); these results agreed with some studies [26, 28]. On the other hand, they were in disagreement with others who found gender differentiation in favor of females [27, 30].
In the present study, the distribution of IL2RA rs11594656 gene polymorphisms revealed that TT, TA, and AA in T1DM patients were frequently observed at ratio of 20%, 60%, and 20% respectively versus 4%, 60%, and 36% in controls with a statistically significant difference (p = 0.045). Obviously, a predominance of TT genotype was seen in patients than controls, and these findings agreed with the studies which reported that IL2RA rs11594656 (TT genotype) as a risk of developing T1D [7, 24, 27, 31], compared to others with opposing results [32,33,34].
Although our results had considered (TT) genotype of IL2RA rs11594656 a significant risk factor of developing T1D regardless of the patients' clinical presentation, reviewing data from past literature showed association of T allele with younger age of onset of T1D [24, 30,31,32,33,34,35,36,37].
While analyzing the distribution of IL2RA rs2104286 gene polymorphisms, findings of the current study showed genotype frequencies as follows: AA, AG, and GG in T1DM patients was 60%, 36%, and 4% respectively versus 57%, 36%, and 7% in controls; these results were of non-statistical significance as shown by p = 0.091. The same was evident as regards the low frequency of A allele of IL2RArs2104286 polymorphism p = 0.86, OR [CI 95% 0.48 (0.19–1.18)]. Our results were found to be in agreement with some related research studies who reported that the studied polymorphism did not display any significant association with T1D [24, 32] in contrast to others that provided evidence for the association between T1D and rs2104286 [7, 31, 37]. Population differences and diversity in the influence of genetic/environmental factors could be claimed for this discrepancy.
In the current study, 11 patients representing 11% of the whole sample of T1D patients were detected to have a homozygous pattern of both IL2RA rs11594656 and IL2RA rs2104286 polymorphisms characterized by positive family history of diabetes (72.6%), poor diabetes control with HbA1C values ranged 8.80–12.30% and mean values of 10.77 ± 1.73, in addition to documented history of recurrent attacks of DKA in 81.8%. These findings may indicate that the conjunction of the homozygous pattern of both IL2RA rs11594656 and IL2RA rs2104286 polymorphisms played an important role in the degree of glycemic control of T1D with the need for further efforts paved towards better life expectancy of those children based on the fact that realized the polygenic nature of T1DM [38, 39].
Although previous studies reported the association between PTPN22 1858 C/T SNP and many autoimmune diseases, Elsisi et al. denied any further evidence that the PTPN22 gene may play a role in the genetic susceptibility to T1D in Egyptian children .
However, a recent Egyptian study reported that T allele of PTPN22 gene and TT genotype of IL2RA were associated with T1D .
This finding was prominent in female patients and those with early onset diabetes. Our study is considered accumulated evidence for the use of these analyzed genes as biomarkers for T1D susceptibility among Egyptian children.
The study was conducted in a relatively small number of patients; so further studies on a larger sample of patients are recommended to confirm our finding. Also, the effect of PTPN22 (C1858T) and IL2RA rs11594656 polymorphisms on diabetes-related antibodies, control of the disease, and insulin requirements should be elucidated in further studies.