RESUMO
OPG/RANK/RANKL axis was reportedly involved in initiating various diseases, especially bone and cardiovascular diseases. This study aimed to assess the relationship between some OPG, RANK, and RANKL polymorphisms and alleles and iron-overload-induced cardiomyopathy in children with transfusion-dependent thalassemia (TDT). This study included 80 TDT children and 80 age and sex-matched controls. Real-time PCR was done for rs207318 polymorphism for the OPG gene and rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, and rs9594782 and rs2277438 polymorphisms for the RANKL gene. Cardiac T2* MRI and ejection fraction (EF) were done to assess the myocardial iron status and cardiac function. In this study, there were no significant differences in frequencies of the studied polymorphisms between cases and controls (p > 0.05 in all). In TDT children, OPG rs2073618 (G > C) had a significant relation to myocardial iron overload (p = 0.02). Its C allele had significantly more frequent normal EF than its G allele (p = 0.04). RANK rs75404403 (C > DEL) had a significant relation to cardiac dysfunction (p = 0.02). Moreover, the C allele of that gene had significantly more frequent affected EF than its DEL allele (p = 0.02). The A allele of RANKL rs2277438 (G > A) had significantly less frequent severe cardiac iron overload than the G allele (p = 0.04). In conclusion, the OPG/ RANK/RANKL genes may act as genetic markers for iron-induced cardiomyopathy in TDT children. Some of the studied genes' polymorphisms and alleles were significantly related to myocardial iron overload and cardiac dysfunction in TDT children.
Assuntos
Cardiopatias , Sobrecarga de Ferro , Talassemia , Humanos , Criança , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único , Talassemia/complicações , Talassemia/genética , Sobrecarga de Ferro/genética , Ferro , Ligante RANK/genéticaRESUMO
OBJECTIVE: To assess the relation of thrombotic markers, thrombomodulin and D-dimer levels to the disease severity in pediatric onset systemic lupus erythematosus (p-SLE) measured by the Systemic Lupus Erythematous Disease Activity Index (SLEDAI). METHODS: 40 children with p-SLE were grouped according to SLEDAI into: low activity SLE group (laSLE) and moderate-high activity SLE group (mhaSLE). 40 healthy children were included as control group. Serum thrombomodulin, and D-dimer levels were measured for all enrolled children. RESULTS: The low activity and moderate-high activity SLE groups had significantly higher mean (SD) thrombomodulin [7.2 (1.83) mg/mL and 9.86 (3.29) mg/mL, respectively vs 5.85 (1.41) mg/mL; P<0.001] and D-dimer (r=0.42, P=0.006) levels than controls. Furthermore, the mhaSLE group had significantly higher thrombomodulin levels and D-dimer (r = 0.42, P= 0.006) levels than the laSLE group (P=0.008 and 0.006). Thrombomodulin and D-dimer had significant positive correlations with SLEDAI. CONCLUSION: Thrombomodulin and D-dimer are valuable markers for p-SLE activity, discriminating children with severe disease activity from those with low disease activity.
Assuntos
Lúpus Eritematoso Sistêmico , Trombose , Criança , Humanos , Trombomodulina , Lúpus Eritematoso Sistêmico/diagnóstico , Trombose/diagnósticoRESUMO
BACKGROUND: RANK/RANKL/OPG axis was implicated in many pathological conditions. The study aimed to assess the relationship between the studied RANK, RANKL, and OPG polymorphisms and alleles and cognitive impairment in children with transfusion-dependent thalassemia (TDT). METHODS: This study included 60 TDT children. Real-time PCR was done for: rs1805034, rs1245811, and rs75404003 polymorphisms for the RANK gene, rs9594782 and rs2277438 polymorphisms for the RANKL gene, and rs207318 polymorphism for the OPG gene. The intelligence quotient (IQ) was assessed using the Wechsler Intelligence Scale for Children-Third Edition. RESULTS: TDT children had a low average total IQ, verbal IQ, and borderline performance IQ. RANK rs1805034 (C > T) had a significant effect on total IQ (p = 0.03). Its TT polymorphism and the CT polymorphism of RANKL rs9494782 (C > T) had a significantly lower total IQ (p = 0.01 for both). The G allele of the RANKL rs2277438 (G > A) had a significantly lower total IQ (p = 0.02). RANK rs1805034 (C > T) and RANKL rs2277438 (G > A) significantly affected verbal IQ (p = 0.01 and 0.03). TT genotype of RANK rs1805034 (C > T) had significantly lower verbal IQ (p = 0.002). Furthermore, the GG genotype of RANKL rs2277438 (G > A) had a significantly lower verbal and performance IQ than the AA genotype (p = 0.04 and 0.01 respectively), and its G allele had a significantly lower performance IQ than the A allele (p = 0.02). CONCLUSION: TDT children had low average total and verbal IQ while their performance IQ was borderline. The RANK/RANKL/OPG pathway affects cognition in TDT children, as some of the studied genes' polymorphisms and alleles had significant effects on total, verbal, and performance IQ of the studied TDT children.