Association of interleukin genes polymorphism with asthma susceptibility in Indian children: a case-control study.

BACKGROUND: Interleukins (IL) 4 and 13 genes and their receptors (R) are the key cytokines which amplify inflammatory reactions in asthma. OBJECTIVE: This study aimed to investigate the association of IL 4, 4 R, 13 and 13 R genes polymorphism with asthma in Indian children. METHODS: In this hospital-based case-control study, included were children aged 1-15 years recruited as diagnosed cases of bronchial asthma, according to EPR 2007 and excluded were subjects with other respiratory diseases. Children with no present or past history of asthma were enrolled as controls. Spirometry was done in cases age ≥ 6 years. Gene-gene interaction was evaluated using binary logistic regression. RESULTS: From October 2010 to July 2013, 275 cases and 275 controls were recruited. Gene-gene interactions between C1112T in IL 13 and Ile50Val in IL 4 R gene polymorphisms were found to be statistically significant (OR = 2.37, 95% CI = 1.04-5.42, p = 0.040). Individuals with CT and GG genotype of C1112T in IL 13 and Ile50Val in IL 4 R were at twice the risk for the development of asthma compared to individuals with both non-risk genotypes. CONCLUSION: The data suggests that gene-gene interactions between IL 13 and IL 4 R genes may play an important role in asthma among Indian children.

CFTR Gene Mutations and Asthma in Indian Children: A Case-Control Study.

Cystic Fibrosis Trans membrane conductance regulator (CFTR) gene is an asthma susceptibility gene. In the present study we investigated the possible association of CFTR gene mutations in Indian asthmatic children as compared to controls. The study included 250 asthmatics and 250 age and sex matched controls. Case to control ratio for sample size was 1:1. Genotyping was performed for 24 CFTR gene mutations by ARMS-PCR and PCR-RFLP method. Among 24 CFTR gene mutations, heterozygous allele of R553X mutation was found in 4 (1.6 %) asthmatic cases and 2 (0.8 %) controls. Value of FVC and FEV1/FVC ratio were significantly lower in heterozygous individuals (p value <0.05). No significant difference was observed in the genotype and allele frequency of R553X mutation (OR = 1.339, 95 % CI = 0.755-2.374, p value = 0.685). Furthermore, all wild type homozygous alleles were observed in remaining 23 CFTR gene mutations. Our data concludes that R553X mutation was not significantly associated in Indian asthmatic children.

Genetic variations of the FCER2 gene and asthma susceptibility in north Indian children: a case-control study.

CONTEXT AND OBJECTIVE: The findings showed that the low-affinity IgE receptor plays a pivotal role in allergic immune response and it is a pharmacogenetic predictor in asthma disease. This study aims to investigate the association of genetic variations: rs28364072 and rs7249320 with asthma and its severity in north Indian children. METHODS: Case-control-based genetic association study was performed among 550 children. RESULTS: Statistical analysis demonstrated significant association between asthma and genotypes frequency of both the SNPs. CONCLUSIONS: Our data indicate that the studied variations are strongly associated with asthma susceptibility and might be risk factor among north Indian asthmatic children.

Maternal and Perinatal Outcome in Patients With Eclampsia: A Study Done at a Tertiary Care Centre.

Background One of the leading causes contributing to morbidity and mortality globally is attributed to eclampsia. Hence, it is vital to comprehensively review each female having eclampsia and to evaluate the factors that govern the outcomes in females with eclampsia. Aim To decode the fetal and maternal outcomes in subjects having eclampsia and to evaluate various factors that govern the outcomes. Methods This retrospective cohort and epidemiological study commenced at the Department of Obstetrics and Gynaecology, Netaji Subhash Chandra Bose Medical College, Jabalpur, Madhya Pradesh, in January 2016 till April 2017, and included females that either developed eclampsia in hospital stay duration or presented with pre-existing eclampsia. In included females, various fetal and maternal parameters were assessed along with the outcome of pregnancy. The institutional data records and the database were also used to determine the prevalence and incidence of eclampsia. Baseline maternal parameters were recorded from the already-existing institute data. These included the gestational age (in years), socioeconomic status, educational attainment, parity, gravidity, and the number of weeks of gestation present at the time of delivery. Antenatal care data assessed were blood pressure recordings, any proteinuria documented in the data, and the number of antenatal visits by the subjects. Statistical analysis was performed to assess both parameters. Results  In the current investigation, there were 0.34% eclampsia cases among females visiting the institution for deliveries. Incidences of stillbirth were seen in 19.04% and 8% of study participants, respectively. We found 9.52% (n=4) of female infants to have perished from eclampsia. Preterm births, a delayed start to the treatment, and insufficient care were all linked to poor foetal and mother outcomes. The longer the period between the beginning of a fit and delivery, the greater the likelihood of unfavourable results. Seizure onset before or after birth, parity, or subject age had no impact on mother or foetal health. The p-value for statistical significance was kept at 0.05. Conclusion Most of the research participant women, had intrapartum eclampsia, postpartum eclampsia, and antepartum eclampsia, based on the time of the convulsions in relation to the labor. It was highlighted that there was no conclusive evidence linking the date of the fit's beginning to unfavourable results or an elevated risk of complications. Neonatal mortality and stillbirth were observed with vaginal delivery in eclampsia cases. Outcomes in eclampsia can be improved by early treatment initiation, timely and appropriate referral, early disease recognition, and appropriate antenatal care.

Association of CFTR gene mutation with bronchial asthma.

Mutation on both the copies of cystic fibrosis transmembrane conductance regulator (CFTR) gene results in cystic fibrosis (CF), which is a recessively transmitted genetic disorder. It is hypothesized that individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary diseases like asthma. There is great heterogeneity in the phenotypic presentation and severity of CF lung disease. This could be due to genetic or environmental factors. Several modifier genes have been identified which may directly or indirectly interact with CFTR pathway and affect the severity of disease. This review article discusses the information related to the association of CFTR gene mutation with asthma. Association between CFTR gene mutation and asthma is still unclear. Report ranges from studies showing positive or protective association to those showing no association. Therefore, studies with sufficiently large sample size and detailed phenotype are required to define the potential contribution of CFTR in the pathogenesis of asthma.

Association of CFTR gene mutation with bronchial asthma and its severity in Indian children: a case-control study.

BACKGROUND: Asthma is a complex genetic disorder. Several genes have been found associated with asthma. The cystic fibrosis transmembrane conductance regulator (CFTR) gene is one of them. AIM: To assess the association of CFTR gene mutation with asthma and its severity as per GINA guidelines. SUBJECTS AND METHODS: This was a hospital-based case-control study. Excluded from cases and controls were those with clinically suspected cystic fibrosis or sweat chloride level>60 mmol/L or suffering from other respiratory diseases. Included were 200 cases and 180 controls, aged 5 months to 15 years. Screening was done for CFTR gene mutations; ΔF508, G542X, G551D, R117H and W1282X using the ARMS-PCR method. RESULTS: ΔF508 was found in three (1.5%) cases and two (1.1%) controls (p = 0.739), G542X in nine (4.5%) cases and five (2.8%) controls (p = 0.374), R117H in one (0.5%) case and one (0.6%) control (p = 0.940) and G551D in twelve (6.0%) cases and two (1.1%) controls (p = 0.012). Individuals carrier for G551D mutation had increased risk for persistent asthma (p = 0.006). Percent predicted FEV1 (p = 0.014) and FVC (p = 0.028) were significantly lower among carriers as compared to non-carriers. CONCLUSION: Significantly higher frequency of G551D mutation among asthma patients compared with controls suggests that this mutation may increase risk for the disease and also its severity.

Higher sweat chloride levels in patients with asthma: a case-control study.

OBJECTIVES: To screen asthmatic patients by sweat chloride test to identify proportion with Cystic Fibrosis (CF); (Sweat chloride level >60 mmol/L). Also, to compare sweat chloride levels between cases of bronchial asthma and age and sex matched healthy children aged 5 mo-15 y. METHODS: The present case-control study was conducted in a tertiary care hospital in India. Cases of bronchial asthma, diagnosed by GINA guideline 2008, and age matched healthy controls were included. Case to control ratio was 2:1. Sweat Chloride test was done by Pilocarpine Iontophoresis method. RESULTS: From April 2010 through May 2012, 216 asthmatics and 112 controls were recruited. Among asthmatics, there was no case of Cystic Fibrosis. Mean sweat chloride levels in asthmatics was 22.39 ± 8.45 mmol/L (inter-quartile range - 15-28 mmol/L) and in controls 19.55 ± 7.04 mmol/L (inter-quartile range - 15-23.5 mmol/L) (p value = 0.048). CONCLUSIONS: No Cystic Fibrosis case was identified among asthmatics. Mean sweat chloride levels were higher in asthmatics as compared to controls.

Spectrum and distribution of CFTR gene mutations in asthma and chronic pancreatitis cases of North Indian population.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) gene accounts for an autosomal recessive condition called cystic fibrosis (CF). In the Indian subcontinent, CF and its related diseases are under-diagnosed by the medical community due to poor knowledge of the disease and its confounding diagnosis, and also due to poor medical facilities available for these patients, thus causing an increased infant mortality rate with a low life expectancy in general. The aim of the study was to document the spectrum and distribution of CFTR mutations in controls, asthma and chronic pancreatitis cases of North India. METHODS: A total of 800 subjects including 400 controls, 250 asthma cases and150 chronic pancreatitis cases were analyzed for 6 mutations (F508del, G542X, G551D, R117H, W1282X, and S549N) and IVS8 Tn polymorphism. RESULTS: Out of 800 subjects, 18% [asthma - 24% (n=250), CP - 29.33% (n=150) cases and controls - 9.3% (n=400)] were positive for heterozygous mutation, 0.8% of the (n=250) asthmatic cases (n=250) were homozygous for IVS8 T5 polymorphism while no subjects were found positive for W1282X mutation. T5 polymorphism was more common in asthmatic cases while F508del mutation in chronic pancreatitis cases. The carrier frequency of F508del, G542X, G551D, R117H, S549N and T5 was 0.015, 0.025, 0.02, 0.005, 0.005, and 0.022 respectively. The cumulative carrier frequency was 0.093. CONCLUSION: CFTR mutations were underestimated in Indian population. The present study will serve in establishment of genetic screening and prenatal setup for Indian population.

Association of S549N and IVS8-5T splice variants with bronchial asthma and its severity in Indian children.

BACKGROUND: Cystic fibrosis transmembrane conductance regulator (CFTR) is an asthma susceptibility gene. Individuals heterozygous for CFTR gene mutation may develop obstructive pulmonary disease like bronchial asthma. AIM AND OBJECTIVE: To find out the association of S549N and IVS8-5T variants of the CFTR gene with bronchial asthma and its severity and to assess the combinational effect of S549N and IVS8-5T variants on severity of disease. MATERIALS AND METHODS: Included were 250 clinically diagnosed bronchial asthma cases aged 5 months to 15 years and 250 age- and sex-matched controls. All cases were further categorized into four different categories as per Global Initiative for Asthma criteria (GINA) guidelines: mild intermittent (83), mild persistent (96), moderate persistent (52), and severe persistent (19). Screening for S549N and 5T variants was done using the polymerase chain reaction-restriction fragment length polymorphism method. RESULT: The proportion of IVS8-5T variant was found significantly higher in cases (10.8%) as compared with controls (2.4%) (p=0.001); however, no significant difference in the proportion of S549N was observed among cases (2.0%) and controls (0.8%) (p=0.447). Individuals mutant for IVS8-5T variant had increased risk for persistent asthma (p=0.000). DISCUSSION: We conclude that IVS8-5T variant is associated with bronchial asthma and can also increase severity of the disease.

Environmental risk factors for persistent asthma in Lucknow.

OBJECTIVE: To identify the risk factors for persistent asthma among common environmental exposures, like ambient air pollutants and second hand smoke, animals, place of residence, decreased ventilation, dust, as well as history of allergic conditions like rhinitis, dermatitis and family history of asthma in children. METHODS: This hospital-based, cross-sectional study was conducted after institutional ethical clearance. Children aged 1-12 y with asthma were recruited after parental consent. Children were classified into asthma severity categories according to GINA 2002 and level of control categories according to GINA 2009 guidelines. Adjusted logistic regression analysis was used to identify factors associated with persistent asthma. RESULTS: From August 2008 through October 2010, 205 asthmatic children were recruited of which 73 (35.60 %) had intermittent and 132 (64.40 %) had persistent asthma. Asthma was controlled in 19 (9.26 %), partly controlled in 90 (43.90 %) and uncontrolled in 96 (46.82 %). Patients with persistent asthma were more likely to have uncontrolled asthma (OR = 8.28; 95 % CI: 2.43-31.01; p < 0.001). Adjusting for age, sex, socioeconomic status and place of residence, persistent asthma was associated with residence within 1.5 km from heavy traffic (OR = 4.58; 95%CI: 2.18-9.59; p < 0.001) and father smoking indoors >5 cigarettes or "bidi"/day (OR = 17.76; 95 % CI: 1.85-170.76; p = 0.01). CONCLUSIONS: Since patients with persistent asthma are more likely to have uncontrolled asthma and since persistent asthma is associated with residence closer to heavy traffic and exposure to second hand smoke, minimizing exposures to these may help in better asthma control.