ABSTRACT
Background/Aims: Statin intolerance leads to poor adherence to statin therapy, resulting in a failure to achieve desired cholesterol reduction and adverse outcomes. The LILRB5 Asp247Gly genotype has been identified as being associated with statin intolerance and statin-induced myalgia. We conducted a randomized clinical trial to examine its role in immune response through T regulatory cell aggregation and in achieving cholesterol reduction targets. Methods: A double-blind, cross-over, recruit-by-genotype trial was undertaken. A total of 18 participants who had either the Asp247Asp (T/T) genotype or the Gly247Gly (C/C) genotype were recruited to the study. Participants were randomised to receive placebo or atorvastatin 80 mg daily for 28 days. Following a washout period of 3 weeks, they were then switched to the opposite treatment. Biochemical and immunological measurements as well as interviews were performed prior to and after both treatment periods. Within genotype group comparisons were performed using repeated measures Wilcoxon tests. Two-way repeated measures ANOVA with genotype and treatment as factors were used to compare changes in biochemical parameters between groups during placebo and atorvastatin periods. Results: Individuals with the Asp247Asp genotype had a greater increase in creatine kinase (CK) compared to those with Gly247Gly genotype in response to atorvastatin (p = 0.03). Those with Gly247Gly genotype had a mean non-HDL cholesterol reduction of 2.44 (95% CI:1.59 - 3.29) mmol/L while in Asp247Asp genotype group the mean reduction was 1.28 (95%CI: 0.48 - 2.07) mmol/L. The interaction between the genotype and atorvastatin treatment for total cholesterol (p = 0.007) and non-HDL cholesterol response was significant (p = 0.025). Immunological assessment showed no significant changes in aggregation of T regulatory cells by genotype. Conclusion: The Asp247Gly variant in LILRB5, previously associated with statin intolerance, was associated with differential increases in creatine kinase and total cholesterol and non-HDL cholesterol-lowering response to atorvastatin. Taken together, these results suggest that this variant could have utility in precision cardiovascular therapy.
ABSTRACT
BACKGROUND: Fluorosis, caused by ingestion of excessive amount of fluoride through food or water, is a major public health problem in India. This study was undertaken to quantify the dental fluorosis burden among school going adolescents and to find factors associated with dental fluorosis in Kolar taluka, Karnataka, India. METHODS: A total of 1026 high school adolescents (12-17 years) were enrolled from different schools selected by stratified sampling method. Dental examination was done to record Dean's fluorosis index, and socio-demographic, food consumption and oral hygiene data were recorded using a pre-tested structured questionnaire. Fluoride content was measured using Orion apparatus, and Community Fluorosis Index (CFI) was calculated from drinking water samples from various drinking sources. Multivariable analysis with generalized estimating equation (GEE) regression model was used to explore the factors associated with dental fluorosis. RESULT: Among 1026 enrolled students, 64.3% of adolescents were detected with dental fluorosis; more than 50% had either severe or moderate fluorosis according to the Dean's Fluorosis Index and Community Fluorosis Index (CFI). The majority of affected students were from government schools. The significantly associated factors with dental fluorosis were living in study area for more than 5 years and studying in government school. A strong positive correlation between the amount of fluoride content in drinking water sample collected and CFI was observed (rho = 0.570). CONCLUSION: Prevalence of dental fluorosis was considerably high, affecting nearly two-thirds of the students, and mainly in government schools and long-term residents of the area. Health education and community awareness for preventing fluorosis, apart from setting-up defluoridation plants or training for home based defluoridation techniques in study villages, should be considered.
