Ashgan A. Alghobashy

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

BACKGROUND Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM. MATERIALS AND METHODS One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA. RESULT Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P=<0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR=2.3, 95% CI=1.3-4.2, P=0.005; OR=2.2, 95% CI=1.1-4.7, P=0.04; OR=1.8, 95% CI=1.03-3.04, P=0.04; OR=4.03, 95% CI=1.2-13.1, P=0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not. CONCLUSION Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.

Synergism of CYP2R1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Egyptian children.

CYP2R1 (25α-hydroxylase) catalyzes vitamin D(3) to 25-hydroxyvitamin D(3), while the CYP27B1 (1α-hydroxylase) catalyzes the 25(OH)D(3) to 1, 25(OH)(2)D(3). 1, 25(OH)(2)D(3) prevents the development of autoimmune diabetes. We aimed to investigate CYP2R1 and CYP27B1 genes polymorphisms and susceptibility to type 1 diabetes in children. One hundred and twenty type 1 diabetic patients and One hundred and twenty controls were genotyped for CYP2R1 (rs10741657) and CYP27B1 (rs10877012) polymorphism. GG genotype of CYP2R1 increased risk to develop type 1 diabetes, and CC genotype of CYP27B1 increased risk to develop type 1 diabetes. Our finding suggested that GG genotype of CYP2R1 polymorphism and/or CC genotype of CYP27B1 polymorphism increased the risk of developing of type 1 diabetes in Egyptian children. In addition there was a synergism between GG genotype of CYP2R1 and CC genotype of CYP27B1 regarding the risk of development of type 1 diabetes.

Oral magnesium supplementation improves glycemic control and lipid profile in children with type 1 diabetes and hypomagnesaemia

Abstract Dietary supplementation with magnesium (Mg) in addition to classical therapies for diabetes may help in prevention or delaying of diabetic complications. We aimed to evaluate the status of serum Mg in children with type 1 diabetes and assessing its relationship to glycemic control and lipid profile. Then evaluating the effect of oral Mg supplementation on glycemic control and lipid parameters. We included 71 children at Pediatric Endocrinology Outpatient Clinic, Zagazig University, Egypt with type 1 diabetes and assessed HBA1c, lipid profile, and serum Mg at the start of study. Patients with serum Mg level < 1.7 mg/dL were given 300 mg Mg oxide for 3 months. After that we reevaluated HBA1c, lipid profile, and serum Mg in all patients. The study included 71 patients with type 1 diabetes (32 males and 39 females); their mean age was 9.68 ± 3.99 years. The mean serum Mg level was 1.83 ± .27 mg/dL. Hypomagnesemia was detected in 28.2% study patients. Serum Mg was found to be positively correlated with high density lipoprotein, mean corpuscular volume and platelet count (P < 0.001), and negatively correlated with age, HbA1c, triglycerides, total cholesterol, low density lipoprotein, and duration of diabetes (P < 0.001). There was significant reduction in HBA1c in group given Mg supplementation. HBA1c was initially 10.11% ± 0.87%. After 3 months of oral Mg supplementation it is reduced to 7.88% ± 0.42% (P < 0.001). There was statistically significant difference in lipid parameters in hypomagnesemic diabetic patients before and after Mg supplementation with significant reduction in serum triglycerides, LDL, and total cholesterol following Mg supplementation with P < 0.001. Although HDL shows a significant increase after Mg supplementation in hypomagnesemic diabetic children with P < 0.001. Correction of hypomagnesemia in type 1 diabetic children with oral Mg supplements is associated with optimization of glycemic control and reduction of atherogenic lipid fraction as well as increase in protective lipid fraction.

The association of PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms with T1D in Egyptian children

BACKGROUND Type 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease characterized by the destruction of pancreatic β cells. PTPN22 and IL2RA polymorphisms have been found to be associated with several autoimmune diseases including T1D. AIMS We aimed to elucidate the role of PTPN22 and IL2RA polymorphisms in predisposition of T1D in Egyptian children. METHODS We studied 150 children and adolescents with T1D and 165 healthy controls. The PTPN22 (rs2476601) and IL2RA (rs11594656) polymorphisms were genotyped using polymerase chain reaction. RESULTS We found that carriers of the T allele of PTPN22 were significantly more likely to develop T1D (OR=2.2, 95% CI=1.2-4, P=0.01). Also, the carrier of TT genotype and T allele of IL2RA more likely to develop T1D (OR=2.8, 1.4, respectively, P=0.03). There was a statistically significant association between T allele of PTPN22 gene and females ⩽10years old at the onset of diabetes (OR=4, 95% CI=1.2-13.4, P=0.019). CONCLUSION This study suggests a possible association between the T allele of PTPN22 gene and TT genotype of IL2RA with T1D in studied Egyptian children, especially, females with early onset diabetes who carried the 1858T allele.

Association of 5-HT2A receptor gene polymorphisms with gastrointestinal disorders in Egyptian children with autistic disorder

Gastrointestinal disturbances (GID) are frequently reported in children with autism spectrum disorders (ASD). Recently, mounting evidence suggests that there may be a genetic link for autism with gastrointestinal disturbances. We aimed to investigate whether there were any association between the -1438A/G, 102T/C and His452Tyr polymorphisms of the serotonin 2A receptor gene (5-HT2A) in Egyptian children with ASD and GID. Eighty children with autistic disorder and 100 healthy control children were examined. -1438A/G, 102T/C and His452Tyr polymorphisms of 5-HT2A were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Significant increase of the G allele and the GG genotype of the -1438A/G polymorphism was observed in children with autism than control, but there were no significant differences in the frequencies either of the 102T/C genotype or His452Tyr genotype between the two groups. There was a significant increase of homozygote A allele of the -1438A/G and CC genotype of the 102T/C polymorphism in ASD children with GID. This study supports the possible involvement of the 5-HT2A receptor in the development of ASD and associated GID.

Trace elements and oxidative stress in children with type 1 diabetes mellitus

Background The early imbalances of trace elements in type 1 diabetes (T1D) may cause disturbance of glucose metabolism and more oxidative stress that may enhance the development of insulin resistance and diabetic complications. We aim to evaluate the serum level of selenium (Se), zinc (Zn), magnesium (Mg), and copper (Cu), the degree of oxidative stress and evaluate their relations to glycemic control in children with T1D. Methods A case–control study which included 100 diabetic children and 40 healthy children age, sex, and ethnicity-matched as a control group. The diabetic children were divided into poor and good controlled patients according to glycosylated hemoglobin (A1c %). Studied children underwent history taking, clinical examination and laboratory measurement of serum Se, Zn, Mg, and Cu levels, erythrocyte reduced glutathione (GSH) and peroxidase enzyme activity (GPx). Results Serum Se, Zn, Mg, Cu, erythrocyte GSH, and GPx were significantly lower in the diabetic group in comparison to the control group (P<0.05) and their levels were lower in poorly controlled patients compared to good controlled patients (P<0.05). The serum Se, Zn, Mg, erythrocyte GSH, and GPx showed a negative correlation with A1c %. The serum Se showed a positive correlation with erythrocyte GSH and GPx ([r=0.56, P<0.001], [r=0.78, P<0.001], respectively). Conclusion Children with T1D, especially poorly controlled cases, had low serum Se, Zn, Mg, Cu, GSH, and GPx. Low serum Se in diabetic children may affect the erythrocyte GSH-GPx system.