Class II major histocompatibility complex in Egyptian type 1 diabetic patients and its predictive value for long term complications

Abstract EN

Background Type 1 diabetes is a complex disease where numerous genes are involved in its pathogenesis.

Epidemiological evidence suggests that genetic factors can affect the course of type 1 diabetic complications independently of glycemic control.

Objective to detect the potential association between human leucocytic antigens (HLA) class II DR and DQ genotypes and the susceptibility to type 1 diabetes and its long term complications among Egyptian population.

Study Design The study was conducted on 130 Egyptian subjects, 60 patients with type 1 diabetes (40 had long term complications) and 70 healthy controls.

For all subjects enrolled into the study the following was done: full history and physical examination, resting ECG, fundus examination, glycemic indices including fasting blood sugar and glycohemoglobin (HbAlc), 24 hours urinary protein excretion, and HLA class II typing (DR & DQ) by microcytotoxcicity test.

Results The frequency of HLA DR4 was significantly higher in Egyptian type 1 diabetic patients (51.6%) compared to healthy controls (30%)(p < 0.05, RR = 2.49).

DR3 was detected in 48.33% of type 1 diabetic patients versus 35% among healthy controls but with no statistically significant difference (p > 0.05, RR = 1.68).

It was also found that DR3/DR4 heterozygosity was significantly higher in Egyptian type 1 diabetics (23.3%) compared to healthy controls (4.3%)(p < 0.01).

The frequency of HLA DR2, DR6 and DR7 were significantly lower in type 1 diabetic patients compared to healthy controls (DR2: 3.3% in diabetics versus 17.1% in controls, p < 0.05 - DR6: 8.3% in diabetics versus 30% in controls, p < 0.01 -DR7: 5% in diabetics versus 20%) in controls, (p < 0.01).

The frequency of DQ4 was significantly higher in Egyptian type 1 diabetics (15%) compared to healthy controls (1.4%)(p < 0.01, RR = 12.1).

However, the frequency of DQ6 was significantly lower in diabetic patients (8.3%) compared to healthy controls (27%)(p < 0.01).

DQ2 and DQ8 in diabetic patients were numerically higher (53% and 36.6% respectively) versus healthy controls (44.2% and 28.8%) respectively) (p > 0.05).

The majority of complicated patients were found to be associated with DR4 and/or DR3.

The frequencies of HLA DR4 and DR3 were 67%) & 50% in diabetic nephropathy, 64%o & 28% in diabetic retinopathy and 48% & 44%) in diabetic peripheral neuropathy respectively.

The frequency of DR4/X was significantly higher in diabetic retinopathy (50%) than those without retinopathy (15.4%) (p < 0.05).

In addition a significantly higher DR5 positivity was detected in Egyptian type 1 diabetic patients with long-term complications (17.5%)(p < 0.05).

DQ4 and DQ7 frequencies were significantly higher in complicated patients versus uncomplicated patients (p < 0.05).

Conclusion It is concluded from the present study that the susceptibility and resistance to type 1 diabetes in Egyptian population are strongly associated with certain HLA class II DR and DQ genes.

DR4 as well as DR4/DR3 heterozygosity are significantly associated with susceptibility to type 1 diabetes, while DR2, DR6, DR7 are protective genes.

On the other hand DQ2, DQ4, DQ8 may be risk factors for such disease, while DQ6 showed a possible protective role.

This study also suggests that the same genes that predispose to type 1 diabetes, specifically those in linkage with DR4 and/or DR3 also predisposes to long term diabetic complications.

In addition, DR5 as well as DQ4 and DQ7 are significantly associated with long-term complications of type 1 diabetes.