Genetic and expression deregulation of immunoregulatory genes in rheumatoid arthritis.

Rheumatoid arthritis (RA) is one of the most common autoimmune diseases globally, and is an important public health concern, associating with early death and systemic complications. Although key development in RA treatment has already been made still RA affected individuals face comorbidity and disability. Therefore, there is a need to discover new risk factors in helping early diagnosis and treatment of RA. The present study is designed to assess the variations of Vitamin D receptor (VDR) and interleukin -6 (IL-6) in RA patients. Polymorphisms of said genes were calculated in 300 RA patients and 300 controls, using Tetra-ARMS polymerase chain reaction. Secondly, expression levels of selected genes were checked using the quantitative PCR (qPCR) and obtained results were evaluated using a different statistical test. Logistic regression analysis showed that frequency of mutant allele of VDR gene polymorphisms (rs11168268, OR = 4.84; 95% CI = 2.94-7.97; p = 0.0001; rs2248098, OR = 1.65; 95% CI = 1.07-2.54; p = 0.02) and IL-6 gene polymorphisms (rs184229712, OR = 2.47; 95% CI = 1.56-3.92, p = 0.0001; rs36215814, OR = 2.14; 95% CI = 1.30-3.53; p = 0.002) was observed significantly higher in RA patients vs controls. Expression analysis showed the significant upregulation of IL-6 (p < 0.0001) and downregulation of VDR gene (p < 0.0001) in RA cases vs controls. ROC curve analysis showed that downregulation of IL-6 (AUC = 0.86, p < 0.001) and upregulation of VDR (AUC = 0.77, p < 0.001) was act as the good diagnostic marker for detection/diagnosis of arthritis. In conclusions, data from the present study showed the significant involvement of VDR and IL-6 gene variations in RA pathogenesis.

Etiology of short stature in children.

OBJECTIVE: To determine the causes of short stature in children with special emphasis on growth hormone deficiency. STUDY DESIGN: Case series. PLACE AND DURATION OF STUDY: Department of Paediatrics, Military Hospital, Rawalpindi and Combined Military Hospital, Multan from September 2004 to January 2007. METHODOLOGY: Two hundred and fourteen children (140 boys and 74 girls), ranging from 02 to 15 years presenting with short stature were studied. Height and weight were plotted on appropriate growth charts and centiles determined. Relevant hematological and biochemical investigations including thyroid profile were done. Bone age was determined in all cases. Growth hormone axis was investigated after excluding other causes. Karyotyping was done in selected cases. Data was analyzed by SPSS 10.0 by descriptive statistics. Mean values were compared using t-test. RESULTS: In this study, the five most common etiological factors in order of frequency were Constitutional Growth Delay (CGD), Familial Short Stature (FSS), malnutrition, coeliac disease and Growth Hormone Deficiency (GHD). In 37.4% of patients, the study revealed normal variants of growth - CGD, FSS or combination of both, 46.7% cases had nonendocrinological and 15.9% had endocrinological etiology. CGD (22.1%) in males and FSS (27%) in females were the most common etiology. GHD was found in 6.1% children and it comprised 38.2% of all endocrinological causes. Children with height falling below 0.4th centile were more likely to have a pathological short stature (79.2%) compared to 39.3% whose height was below 3rd centile but above 0.4th centile (p < 0.05). CONCLUSION: CGD and FSS are most common causes of short stature in boys and girls respectively, whereas, GHD is a relatively uncommon etiology.