Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level

(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730С (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730С gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14–7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05–3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09–2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08–0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07–0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74–5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.

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Osteoporosis in multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458510368985 ◽

2010 ◽

Vol 16 (9) ◽

pp. 1031-1043 ◽

Cited By ~ 47

Author(s):

Andrew P Hearn ◽

Eli Silber

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Bone Mineral Density ◽

Bone Mineral ◽

Significant Risk ◽

Mineral Density ◽

Increased Risk ◽

Review Management ◽

Multiple Sclerosis Patients ◽

Reduced Mobility

Fractures resulting from osteoporosis are a major cause of morbidity and mortality in the developed world. People with multiple sclerosis experience reduced mobility and are susceptible to falls. Glucocorticoid use and reduced mobility are known risk factors for osteoporosis. This paper is a review of osteoporosis in people with multiple sclerosis, looking at its prevalence, risk factors and possible mechanisms. We also review management guidelines for osteoporosis in the general population and use these to propose guidelines for osteoporosis management amongst multiple sclerosis patients. A number of studies have examined the incidence of reduced bone mineral density amongst people with multiple sclerosis; the majority provide convincing evidence that bone mineral density is significantly reduced in multiple sclerosis patients. The most significant risk factors appear to arise from the chronic disease process of multiple sclerosis and not from glucocorticoid use. There are currently no guidelines or consensus as how best to treat osteoporosis amongst multiple sclerosis patients despite their being at an increased risk. We propose an algorithm for the screening and treatment of osteoporosis in people with multiple sclerosis.

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Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis

BMC Neurology ◽

10.1186/s12883-019-1577-y ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 7

Author(s):

Danyal Imani ◽

Bahman Razi ◽

Morteza Motallebnezhad ◽

Ramazan Rezaei

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Gene Polymorphisms ◽

Genetic Model ◽

Meta Analysis ◽

Case Control ◽

Case Control Studies ◽

Asian Populations ◽

Increased Risk ◽

Apai Polymorphism

Abstract Background The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. Method All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). Results A total of 30 case–control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01–1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. Conclusion This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene–environment and gene–gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

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A study of risk factors for catheter associated urinary tract infection

International Journal of Advances in Medicine ◽

10.18203/2349-3933.ijam20180525 ◽

2018 ◽

Vol 5 (2) ◽

pp. 334 ◽

Cited By ~ 3

Author(s):

Leelakrishna P. ◽

Karthik Rao B.

Keyword(s):

Risk Factors ◽

Urinary Tract ◽

Closed System ◽

Univariate Analysis ◽

Significant Risk ◽

P Value ◽

Indwelling Catheters ◽

Increased Risk ◽

Catheter Size ◽

Tract Infections

Background: Catheter associated urinary tract infections (CAUTIs) are the most common causes of UTIs in postoperative cases. Many risk factors are associated with its incidence. The present study was conducted with the aim to determine the related risk factors and to identify the causative agents contributing to the urinary tract infection.Methods: This prospective study was conducted on 210 patients meeting the requirements of inclusion criteria during September 2012 to February 2014. Detailed history of the patients was recorded. Urine culture was done at different time intervals to identify the causative agent suggestive to CAUTI. Univariate analyses of the association of each variable with CAUTI and multivariable logistic regression were done to predict CAUTI outcome.Results: The mean age of study participants was 51.61 years. Among them 141 were males and 69 were female patients. On univariate analysis purpose for urine catheterization, place of catheterization, breach in the closed system of drainage, duration of catheterization, hemoglobin value less than 10, raised renal parameters with serum creatinine more than 1.5 were all significantly associated with development of CAUTI (p value 0.000). Sex of the patient (p value 0.279) and catheter size (p value 0.279) was not found to have a significant correlation with increased risk of CAUTI. On multivariate analysis, age, catheter size, diabetes, duration of catheterization, a breach in the closed system of catheter drainage and sex were found to be the significant risk factors associated with CAUTI (p<0.05).Conclusion: An understanding of the risk factors in development of CAUTI, significantly helps in reducing the additional burden on the health care system. Measures such as shortening the duration of catheterization, strict control of diabetes and sterile precautions in insertion and maintenance of indwelling catheters can help in prevention CAUTI.

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Differential DNA Methylation by Hispanic Ethnicity Among Firefighters in the United States

Epigenetics Insights ◽

10.1177/25168657211006159 ◽

2021 ◽

Vol 14 ◽

pp. 251686572110061

Author(s):

Jaclyn M Goodrich ◽

Melissa A Furlong ◽

Alberto J Caban-Martinez ◽

Alesia M Jung ◽

Ken Batai ◽

...

Keyword(s):

Dna Methylation ◽

Pilot Study ◽

The United States ◽

P Value ◽

Q Value ◽

Blood Leukocytes ◽

Cpg Sites ◽

False Discovery ◽

Increased Risk ◽

Hispanic White

Firefighters are exposed to a variety of environmental hazards and are at increased risk for multiple cancers. There is evidence that risks differ by ethnicity, yet the biological or environmental differences underlying these differences are not known. DNA methylation is one type of epigenetic regulation that is altered in cancers. In this pilot study, we profiled DNA methylation with the Infinium MethylationEPIC in blood leukocytes from 31 Hispanic white and 163 non-Hispanic white firefighters. We compared DNA methylation (1) at 12 xenobiotic metabolizing genes and (2) at all loci on the array (>740 000), adjusting for confounders. Five of the xenobiotic metabolizing genes were differentially methylated at a raw P-value <.05 when comparing the 2 ethnic groups, yet were not statistically significant at a 5% false discovery rate ( q-value <.05). In the epigenome-wide analysis, 76 loci exhibited DNA methylation differences at q < .05. Among these, 3 CpG sites in the promoter region of the biotransformation gene SULT1C2 had lower methylation in Hispanic compared to non-Hispanic firefighters. Other differentially methylated loci included genes that have been implicated in carcinogenesis in published studies ( FOXK2, GYLTL1B, ZBTB16, ARHGEF10, and more). In this pilot study, we report differential DNA methylation between Hispanic and non-Hispanic firefighters in xenobiotic metabolism genes and other genes with functions related to cancer. Epigenetic susceptibility by ethnicity merits further study as this may alter risk for cancers linked to toxic exposures.

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Characteristics of SARS-CoV-2 positive and complicated COVID-19 patient cohorts in Israel: A comparative analysis

10.1101/2020.05.07.20091652 ◽

2020 ◽

Cited By ~ 3

Author(s):

Chen Yanover ◽

Barak Mizrahi ◽

Nir Kalkstein ◽

Karni Marcus ◽

Pinchas Akiva ◽

...

Keyword(s):

Risk Factors ◽

Kidney Diseases ◽

Significant Risk ◽

P Value ◽

Public Health Policies ◽

Global Pandemic ◽

Increased Risk ◽

Risk Patients ◽

Risk Of Disease

AbstractReliably identifying patients at increased risk for COVID-19 complications could guide clinical decisions, public health policies, and preparedness efforts. The most globally accepted definitions of at-risk patients rely, primarily, on epidemiological characterization of hospitalized COVID-19 patients. However, such characterization overlooks, and fails to correct for, the prevalence of existing conditions in the wider SARS-CoV-2 positive population. Here, we use the complete medical records of 4,353 Israeli SARS-CoV-2 positive individuals, of whom 173 experienced moderate or severe symptoms of COVID-19, to identify the conditions that increase the risk of disease complications, in various age and sex strata. Our analysis suggests that cardiovascular and kidney diseases, obesity, and hypertension are significant risk factors for COVID-19 complications, as previously reported. Interestingly, it also indicates that depression (e.g., odds ratio, OR, for males 65 years or older: 2.94, 95% confidence intervals [1.55, 5.58]; P-value = 0.014) as well cognitive and neurological disorder (e.g., OR for individuals ≥ 65 year old: 2.65 [1.69, 4.17]; P-value < 0.001) are significant risk factors; and that smoking and background of respiratory diseases do not significantly increase the risk of complications. Adjusting existing risk definitions following these observations may improve their accuracy and impact the global pandemic containment efforts.

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Association of Interleukin 7 Receptor (rs1494555 and rs6897932) Gene Polymorphisms with Asthma in a North Indian Population

Allergy & Rhinology ◽

10.2500/ar.2015.6.0137 ◽

2015 ◽

Vol 6 (3) ◽

pp. ar.2015.6.0137 ◽

Cited By ~ 1

Author(s):

Shweta Sinha ◽

Jagtar Singh ◽

Surinder Kumar Jindal

Keyword(s):

Indian Population ◽

Receptor Gene ◽

Significant Risk ◽

Nucleotide Polymorphisms ◽

North Indian Population ◽

Protective Association ◽

Interleukin 7 ◽

Increased Risk ◽

Α Chain ◽

Primer Polymerase Chain Reaction

Background Interleukin 7R (IL-7R), a cytokine receptor gene, plays an important role in the development of innate and adaptive inflammatory response in asthma etiology. Objective IL-7R is a heterodimeric protein composed of α chain and γ chain. The α chain of IL-7R has a range of single nucleotide polymorphisms, which give rise to nonsynonymous amino-acid substitutions that might result in an increased production of inflammatory cytokines and cause asthma. Methods A case-control study was conducted with a total of 964 subjects, including 483 healthy controls and 481 patients with asthma. DNA samples were extracted from blood, and genotyping was done by using sequence-specific-primer–polymerase chain reaction. Results Statistical analysis revealed that IL-7R + 1237A/G (rs1494555) gene polymorphism shows a highly protective association toward asthma (odds ratio [OR] 0.56, p < 0.001) in AG genotype as well as in mutant GG genotype (OR 0.64, p = 0.029). However, IL-7R + 2087T/C (rs6897932) polymorphism showed an increased risk toward asthma in TC genotype (OR 1.70, p = 0.002) as well as in the CC genotype (OR 1.68, p = 0.002). Furthermore, the GT and AC haplotypes in the IL-7R polymorphisms were also found to be significantly associated with asthma (p = 0.001 and p = 0.037, respectively). Conclusions The study conducted in a north Indian population indicated that the protective association was observed for the + 1237A/G position, and a significant risk was observed for the + 2087T/C position in asthma.

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Association between Vitamin D receptor gene polymorphism and the risk of Multiple Sclerosis: Systematic review and meta-analysis

10.21203/rs.2.17139/v1 ◽

2019 ◽

Author(s):

Danyal Imani ◽

Bahman Razi ◽

Morteza Motallebnezhad ◽

Ramazan rezaei

Keyword(s):

Multiple Sclerosis ◽

Vitamin D ◽

Gene Polymorphism ◽

Vitamin D Receptor ◽

Subgroup Analysis ◽

Large Scale ◽

Meta Analysis ◽

Receptor Gene ◽

Asian Population ◽

Increased Risk

Abstract Background The association between the vitamin D receptor ( VDR ) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several studiese. However, the findings were inconsistent and inconclusive.Methods All relevant studies reporting the association between the FokI (rs2228570) or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms of the VDR and susceptibility to multiple sclerosis published up to September 2019 were identified by comprehensive systematic database search in web of science, Scopus, and PubMed.Results A total of 30 case–control studies were included in this meta-analysis. The overall results suggested a significant association between TaqI gene polymorphism and MS risk under heterozygote contrast (OR = 1.27, 95%CI = 1.01–1.59, REM). Moreover, the pooled results of subgroup analysis decline presence of significant association under all defined genotype model. In subgroup analysis, BsmI gene polymorphism was associated with increased risk of MS under the recessive model in Asian population. In other hand, ApaI gene polymorphism was associated with decreased risk of MS under recessive and homozygote contrast (aa vs AA) models in Asian population.Conclusions This meta-analysis suggested a significant association between TaqI gene polymorphism and MS susceptibility. Furthermore, BsmI gene polymorphism was associated with an increased risk of MS in Asian population. In contrast, ApaI gene polymorphism was associated with a decreased risk of MS in Asian population. Future large scale studies on gene–environment and gene– gene interactions are required to estimate related risk factors and assist early diagnosis of patients at high risk for MS.

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Respiratory distress in vigorous babies born through meconium stained amniotic fluid: incidence, onset, risk factors and predictors at birth

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20170461 ◽

2017 ◽

Vol 4 (2) ◽

pp. 390

Author(s):

Kulkarni Poornima Prakash ◽

Shilpa Dinesh B. K.

Keyword(s):

Risk Factors ◽

Caesarean Section ◽

Respiratory Distress ◽

Amniotic Fluid ◽

Significant Risk ◽

P Value ◽

Perinatal Risk Factors ◽

Perinatal Risk ◽

Increased Risk ◽

Meconium Stained Amniotic Fluid

Background: One in every seven pregnancies ends with meconium-stained amniotic fluid (MSAF). MSAF can be harmful to the newborn with short and long-term sequelae. This study was aimed to find out the incidence, predictors, onset and severity of respiratory distress among vigorous babies born through meconium stained amniotic fluid which may or may not be evident at birth.Methods: It is a prospective observational study. One hundred forty-one neonates were studied. Data was collected on perinatal risk factors, clinical course and development of respiratory distress. Significance of the perinatal risk factors were identified by fisher’s exact test (p-value) and score based on odds ratio was assigned for significant risk factors. Results: This study included one hundred and forty-one vigorous babies born through meconium stained amniotic fluid, of which 36.9% (52) babies developed respiratory distress. Of the 52 babies who developed respiratory distress 19.23%(10 babies) developed meconium aspiration syndrome (MAS). In our study, it was observed factors like caesarean section and thick meconium increased risk of respiratory distress in the neonates born through meconium stained amniotic fluid who were vigorous.Conclusions: The incidence of respiratory distress in vigorous babies born through meconium stained liquor in this study was observed to be 36.9% (52 babies). 98.07% (51 babies) developed respiratory distress at birth or within one hour of life. All the babies who developed MAS had mild or moderate form of MAS. None of the babies required assisted ventilation. Risk factors like thick meconium, caesarean section showed significant increase in the incidence of respiratory distress. Therefore intrapartum monitoring and timely intervention can prevent the complications of MAS.

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A study on role of thrombocytopenia in retinopathy of prematurity

International Journal of Contemporary Pediatrics ◽

10.18203/2349-3291.ijcp20200106 ◽

2020 ◽

Vol 7 (2) ◽

pp. 346

Author(s):

Aswathy Benedict ◽

Mario Joseph Bukelo

Keyword(s):

Risk Factor ◽

Retinopathy Of Prematurity ◽

Tertiary Care ◽

Significant Risk ◽

P Value ◽

Care Hospital ◽

Hospital Data ◽

Retrospective Case ◽

Oxygen Exposure ◽

Increased Risk

Background: Retinopathy of Prematurity (ROP) is one of the causes of avoidable blindness in India. Globally ROP is estimated to affect more than 50,000 infants annually and in India, every year, 500 children are estimated to become blind from ROP. Many a times, lack of trained professionals and lack of timely referral are found to be setbacks in ROP diagnosis and treatment in developing nations. The aim of the study was to study if thrombocytopenia is a risk factor for retinopathy of prematurity and does supplemental oxygen with thrombocytopenia increases the risk of ROP.Methods: It was a retrospective case control study done in a tertiary care hospital. Data was collected from 177 preterm admitted to NICU over a period of 3 years from March 2015-2018.Results: A total of 177 preterm admitted to the NICU was included in this study. 77 had ROP and were taken as cases, while 100 were controls. Out of the cases, 55.6% had thrombocytopenia (OR-2.47, p value: 0.003). 89% (n =69) of cases had significant oxygen exposure (OR-8.65, p value 0.0001; 95% CI: 2.00-10.75). Oxygen exposure and thrombocytopenia coexisted in 57% of cases, with 4 times increased risk of ROP (OR-4.51, p value: 0.0001).Conclusions: Thrombocytopenia is a significant risk factor for retinopathy of prematurity in preterm. The presence of thrombocytopenia with significant oxygen exposure tends to accentuate the risk further. Future prospective studies with long term follow up are warranted to establish other risk factors.

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A prospective observational study to determine the utility of placental laterality for prediction of preeclampsia in pregnancy

International Journal of Reproduction Contraception Obstetrics and Gynecology ◽

10.18203/2320-1770.ijrcog20201241 ◽

2020 ◽

Vol 9 (4) ◽

pp. 1664

Author(s):

Anshul Rana ◽

Rama Thakur ◽

Rohini Rao

Keyword(s):

Mode Of Delivery ◽

Previous History ◽

Significant Risk ◽

P Value ◽

Large Sample Size ◽

Multisystem Disorder ◽

Fetal Outcomes ◽

Hypertension In Pregnancy ◽

Increased Risk ◽

In Pregnancy

Background: Preeclampsia is a multisystem disorder of unknown aetiology and recently its link with placental laterality has been explored. The objective of this study was to find the association of placental laterality with maternal and fetal outcomes in pregnancy. Study also determined the predictive ability of placenta laterality for the development of hypertension in pregnancy.Methods: A prospective observational cohort study was conducted on 200 pregnant women. Routine investigations and doppler analysis were done. Placenta position was categorized into central and lateral. Maternal and fetal outcomes were recorded. The data was entered in MS excel spreadsheet and analysis was done using statistical package for social sciences (SPSS) version 21.0. A p value of < 0.05 was considered statistically significant.Results: Study found no significant association of placental laterality with hypertension in pregnancy. Various fetal complications, birth weight, Apgar scores and NICU admission were comparable among women with central or lateral placenta (p > 0.05). Even the maternal outcomes like mode of delivery, onset of labor, indication of labor induction and caesarean deliveries were comparable among women with central or lateral placenta (p > 0.05). On applying univariate logistic regression analysis, previous history of hypertension in pregnancy was a significant risk factor for development of preeclampsia with odds ratio of 168.43 (p < 0.05).Conclusions: It can be concluded that the maternal and fetal outcomes are independent of the placenta laterality. The doppler characteristics and placenta laterality did not show any increased risk for hypertension in pregnancy. However future studies are recommended with large sample size including more women with diagnosed hypertension in the pregnancy so that a better association can be derived with placenta laterality and doppler characteristics.

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