T2DM usually becomes clinically apparent after 40 years of age [13]. T2DM seriously affects patients' quality of life and imposes a huge economic burden on national health and economy [8].
In recent years, evidence has revealed that T2DM may be due to the disorder of the natural immune system and is associated with chronic inflammation. In some studies, T2DM has been described as a disease caused by chronic inflammation, and this pathogenic role of inflammation in diabetes has been proven by many studies [14–16]. Inflammation biomarkers such as TNF-alpha, IL-6 and C-reactive protein have been reported to predict the development of T2DM [16, 17]. It has also been stated that proinflammatory cytokines can cause insulin resistance by inhibiting the transmission of insulin signal in skeletal muscle, liver and adipose tissue [18]. Another study has stated that such cytokines increase the risk of T2DM by increasing insulin resistance in fat and other tissues [19]. Three single nucleotide polymorphisms of the IL-6 promoter at positions − 174 (rs 1800795), -572 (rs 1800796) and − 597 (rs 1800797) can cause an interpersonal change in the transcription and expression of IL-6 [13, 20].
In this study, we found IL-6 gene rs 1800796 polymorphism to be significantly different between the control group and the T2DM patient group. The CC genotype was rare, but there was no statistically significant difference between DN + and DN- (Table 3).
In accordance with our results, in the study conducted by Wang et al., the prevalence of IL-6 gene rs 1800796 GG genotype was 4.7% in T2DM patient group and 1.84% in the control group. There was a significant difference between the two groups; based on these data, they reported that the risk of T2DM might be high in the IL-6 gene rs 1800796 GG genotype [21]. Yin et al. showed that there is a significant relationship between the IL-6 gene rs 1800796 G allele and the increased T2DM risk [8]. As a result of the allele model of the researchers, the risk of developing T2DM in G allele carriers has proved to be 1.29 times higher than in the C allele. It has also been reported that individuals with the GG genotype have a significantly higher risk of developing T2DM compared to the GC genotype or the CC genotype. Furthermore, these researchers have suggested that SNPs at this location may be seen as candidate biomarkers for T2DM screening, diagnosis and treatment in the future [8]. Regarding rs 1800796 single nucleotide polymorphism, in a study among Caucasian Danish subjects, a significant increase in the risk of developing T2DM was shown to those carrying the C allele [7, 22].
In their study with healthy pregnant women and pregnant women with gestational diabetes in Mongolia, Zang et al. found IL-6 rs 1800796 frequencies to be CC (21.67%), CG (37.50%) and GG (40.83%), allele frequencies to be C (40.42%) and G (59.58%). They found the distribution frequencies of IL-6 rs 1800796 in gestational diabetes to be CC (19.29%), CG (54.29%) and GG (26.43%), allele frequencies to be C allele (46.43%) and G allele (53.57%). Based on their results, they reported that there was no significant difference between pregnancies with gestational diabetes and healthy pregnancies in terms of IL-6 rs1800796 genotypes or allele frequency [23].
Unlike our study results, in their study with the Bangladeshi participants, Pandaya et al. stated that IL-6 rs 1800796 polymorphism was not related to T2DM. Also; Pandaya et al. were reported that the circulating level of IL-6 remains elevated in people with type 2 diabetes and furthermore, this value serves as an indirect measure for the condition of insulin resistance [24].
In our study, no significant difference was found between the patients with and without DN in terms of IL6 gene rs1800796 polymorphism genotype numbers and percentages and allele numbers and percentage values (Table 3).
There are also studies that yielded different results from ours. In their study, Chen et al. reported that IL-6 gene promoter rs1800796 polymorphism is associated with type 2 DN, and the G allele may be a genetic risk factor for type 2 DN. Also, they stated that the G allele may increase the risk by increasing IL-6 expression in the pathogenesis of type 2 DN [25]. Another study conducted by Chang et al. showed that in general, rs1800796 GG and rs1524107 CC homozygous genotypes may pose a higher risk for the development of nephropathy in T2DM [11].
Kitamura et al. conducted a study with Japanese patients with T2DM and stated that IL-6 rs1800796 polymorphism may be associated with and responsible for the progression of DN. They also reported that GG genotype requires confirmation of the effect of DN on the development/progression with a large-scale prospective study [9].
Pradhan et al. In their studies; reported that IL-6 levels in female patients with type 2 diabetes were statistically different compared to controls [15]. Unlike our results, in other studies were conducted with patients with type 2 diabetes, IL-6 levels were found to be statistically different in the control and patient groups [12, 14].