Association of CRP Haplotypes in Rheumatoid Arthritis and their Correlation with Severity of the Disease.

BACKGROUND: Rheumatoid arthritis is a heterogenous autoimmune disorder of unknown cause with variable clinical expression. Genetic factors play an important role and likely account for about 60% of disease susceptibility and expression. The aim of this study to find out the association of CRP haplotypes in rheumatoid arthritis and their correlation with severity of the disease. MATERIAL AND METHODS: This was case control study where in all available patients and volunteers (only for blood samples) were recruited. Peripheral blood samples of patients were collected at Rheumatology Clinic and Medicine Department of S.P. Medical College, Bikaner in collaboration with Department of Biological Sciences, BITS, Pilani-Hyderabad during July 2009 to January 2012. 100 control subjects with no known history of disease and 135 cases were recruited as per pre-decided inclusion and exclusion criteria. A tag SNP approach captured common variation at the CRP locus and the relationship between genotype and serum CRP was explored by linear modelling. RESULTS: Cases comprised of 98 females (Mean age 43.01+13.23 yrs) and 37 (mean age 47.4+14.9 years) males. The Control group comprised of 100 unrelated healthy controls. The cases and controls did not differ significantly for any of the clinical parameters, except for serum CRP levels. The allele distribution of rs1205 polymorphism among the studied cases and controls, which was statistical non-significant. The rs3093066 polymorphism located at the 3` position of the gene in the UTR at position number 157949723. The rs3116640 polymorphism located at 157948938 position on chromosome1 and the allele distribution of rs3116637 polymorphism among cases and controls which was also found to be monomorphic respectively. CONCLUSION: Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients. Genetic studies can also impact strategies adopted for effective personalized treatment for this progressively debilitating disease.

Frequency and Predictors of Pacifier Use in the Low Socioeconomic Group of Karachi, Pakistan: A Cross-Sectional Study.

Background Pacifier use has been popular for ages. They are prevalent all over the world because of their various perceived benefits. On the other hand, there is a common belief that they do carry health risks as well. Due to these contradicting belief systems, the frequency of their use, and the factors that determine them, need to be thoroughly evaluated. Since Pakistan is a developing country with a low literacy rate, it can be implied that a vast majority of the country's population may lack awareness regarding the advantages and disadvantages of pacifier use, making them incapable of weighing associated risks versus benefits. The data evaluating these factors in this region are however scarce in the published literature. We, therefore, aimed to highlight the frequency and predictors of pacifier use in the low socioeconomic group of Karachi, Pakistan. Materials and methods A descriptive, cross-sectional study was conducted on a sample of 300 mothers visiting a tertiary care hospital in Karachi, Pakistan. We included mothers who had at least one child under the age of two years, and whose child did not have any oro-nasal anomaly that could prevent them from sucking a pacifier. Data were collected using pre-tested questionnaires and analyzed using the Statistical Package for Social Sciences (SPSS version 23.0, IBM Corp., Armonk, NY, US). Frequencies were calculated and presented in the form of tables. The chi-square test was used to determine the significance of all categorical variables. A P-value of <0.05 was considered to be statistically significant. Results Almost half of our respondents (49%) gave pacifiers to their children. A significant number (59%) of these mothers were uneducated. Almost all (97%) of the users had annual household income less than 15,000 Pakistani rupees (PKR); 34% were primiparous and more than two-thirds (71%) had a normal vaginal delivery. Out of all the factors, maternal age less than 20, annual household income less than 15,000 PKR, and primiparity were significantly associated with pacifier use in mothers (P<0.05). Only a half of the users (51%) cleaned the pacifiers by boiling; one-fourth (25%) washed it with water only; while 18% washed it with soap and water. The majority (84%) of the mothers used the pacifier to soothe the baby when upset. Among mothers who did not use a pacifier, about a third (30%) did not do so as they believed it's a bad practice. About one-fourth (27%) believed it was unhygienic. Conclusions Our study highlights the gap in the awareness of mothers regarding pacifier use. Using this data, we can target to disseminate specific information to this population to integrate safe and healthy child care habits in society.

Study of APOE Gene and D2S439 Marker in Patients of Rheumatoid Arthritis and their Correlation with Severity of Disease: A Case Control Study.

AIM: To delineate the genetic differences in polymorphism of the APOE and D2S439 marker genes for patients with and without rheumatoid arthritis and to study the distribution frequency of the prevalent alleles of these genes in clinically defined sub groups of patients/controls of Indian origin, specifically and their correlation with severity of disease using DAS score. MATERIAL AND METHODS: This is a case control study where peripheral blood samples 160 cases and 150 controls were collected. RESULTS: We evaluated the association of the tetra nucleotide repeat microsatellite marker D2S439 lying at 231.27cM position on the q arm of chromosome-2. The alleles of this marker ranged in size from 163bp-203bp in PCR product length corresponding to 5-15 (CTAT)n tetra repeats. The allele frequencies for this marker in the North Indian population are different from the CEPH populations. The longer alleles, >199bp (=14 or 15 CTAT repeats) were not observed. The genotypes after bimodal distribution differ significantly among cases and controls (p=0.003). Statistically significant difference was seen between cases and controls for ≥(CTAT) 10 longer allele which was more prevalent in the adult RA cases than in controls. Severity of RA was defined by a DAS28 score of >6 on a scale of ten. No significant association was seen with the APOE polymorphism and disease severity. CONCLUSION: The long allele of D2S439 marker representing an expansion of the CTAT, tetranucleotide repeat doubles an individual's the risk for developing RA.

Role of µ-Opioid Receptor Polymorphism in Patients of Rheumatoid Arthritis and their Correlation with Severity of Disease.

INTRODUCTION: With 1 billion tobacco users worldwide, nicotine dependence has a major impact on global health. Advances in medication development for nicotine dependence require an improved understanding of the neurobiology of this complex, relapsing brain disorder. AIMS: To study association of µ Opioid Receptor polymorphism in patients of rheumatoid arthritis and its correlation with severity of disease and prevalent alleles of the OPRM1 genes. MATERIAL AND METHODS: This is a case control study wherein all available patients and volunteers were recruited. 142 controls subjects with no known history of disease and 85 study group cases were included. RESULTS: Comparison of genotype frequencies showed a statistically significant difference between the studied groups (p<0.004). A statistically significant difference was found when the allelic frequencies between the two groups were compared (p<0.0001), with the 17T allele having a-1.7518 fold higher risk of having RA (risk ratio (RR)=1.7518, 95%CI of RR=1.2988-2.3627, OR =3.2914; 95%CI =1.9608-5.5251). Significant difference was also found when the allelic frequencies between the two groups were compared (p<0.0001), with the 118G allele having a 1.5-fold higher risk of developing RA (RR)=1.5801, 95%CI =1.3091-1.9071, OR=3.1357; 95%CI 2.1083-4.6638). CONCLUSION: The study definitely needs to be extended to larger cohort of patients and control samples and to a larger set of candidate µ opioid receptors. Extending the studies to a larger cohort will also allow genetic analyses of clinically defined endophenotypes observed in the patients of this chronic metabolic disease with attributes of autoimmune disorder and multiple symptoms in patients.

Study of Bone Mineral Density (BMD) in Patients with Rheumatoid Arthritis and its Co-relation with Severity of the Disease.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic inflammatory disease of unknown etiology marked by a symmetric, peripheral polyarthritis.1-3 People with rheumatoid arthritis are at increased risk of osteoporosis. Hence this article intends to highlight the importance of BMD measurement in patients with RA as a tool for assessment of disease activity and severity. OBJECTIVE: To evaluate Bone Mineral Density in patients of Rheumatoid Arthritis and Co-relate it with severity of disease. MATERIAL AND METHODS: Hand bone density was measured on the plain radiographs of the right hand using digital x-ray radiogrammetry (Pronosco Xposure System 2.0). This BMD was correlated with markers of disease activity using DAS 28 Scoring system.4. RESULTS: In our study there were 200 patients with equal number of controls. 70 patients in study group and 131 patients in control group were <45 years old and had normal Z-score while in age group >45 years 26 and 20 cases in study and control groups respectively had their Z-score within normal range. There were total 21 and 2 cases of study and control groups respectively (age <45 years) who had osteoporosis while in age group >45 years 12 and 10 cases in study and control groups respectively had osteopenia. CONCLUSIONS: Patients with RA are more susceptible for bone loss in comparison to normal age and gender related subjects. Patients with longer duration and higher disease activity are more susceptible for developing osteopenia and osteoporosis. Occurrence of joint deformities increases with longer disease duration. Limitation of physical activity impairs the bone mineral density. Patient taking anti-rheumatic therapy (steroids and Disease-modifying antirheumatic drugs) are at increased risk of bone loss. All these factors contribute to bone loss independent of each other.

A Study of Genetic Markers in Patients of Rheumatoid Arthritis and their Co-Relation with Severity of the Disease.

INTRODUCTION: Dyslipidemia has been reported to attribute to early death due to increased atherosclerosis leading to CVDs in patients with RA. Recent reports have suggested a role of adipocytokines in mediating joint damage rheumatoid arthritis (RA). RA has long been associated with increased cardiovascular risk as atherosclerosis is more prevalent in patients of RA than in the general population. Specific alleles of APOE gene have been reported to be associated with risk for atherosclerosis and LEP gene alleles have been associated with increased BMI. We evaluated the association of polymorphisms in the APOE and the LEP gene, with risk for developing RA and severity of joint damage in patients with RA. MATERIAL & METHODS: Peripheral blood samples from age and ethnicity matched healthy controls and RA patients, recruited for the study, were collected and used for DNA isolation and allele typing for D7S1875 (LEP gene) and APOE using PCR-LP/RFLP based method reported in literature4,5 followed by data analysis using Medcalc. RESULTS AND CONCLUSIONS: Based on the findings of this study no correlation was seen between RA and LEP gene (D7S1875) allele/genotypes. It was seen that the APOE*4 allele was more prevalent in controls than in cases indicating that this allele is probably playing a significant protective role (p=0.0002, OR=0.3336, CI:0.1856-0.5997) as opposed to the other two Apo E alleles. The Apo E*3 allele was the most prevalent allele in both cases and controls which is similar to earlier reports from several different groups. No significant association was observed between the APOE genotype and the DAS28 score. Finally, it can be concluded that while the short allele of the D7S1875 (LEP gene) marker increases the risk for developing RA (OR=1.72, p=0.038) the APOE*4 allele seems to play a protective role in RA (OR=0.3336, p=0.0002).