NLRP3 Rs35829419 Research Articles

Association of polymorphism of NLRP3, ICAM-1, PTPN22, INS genes in childhood onset type 1 diabetes in a Pakistani population.

Type 1 diabetes (T1D) is an organ-specific autoimmune disorder characterized by the destruction of pancreatic β cells, leading to absolute insulin deficiency. The genes NLRP3, ICAM-1, PTPN22, and INS are reportedly associated with T1D in other populations. However, the genetic pattern of T1D in the Pakistani population is not clear. This study aimed to find the association of polymorphisms in the PTPN22, INS, NLRP3, and ICAM-1 genes with T1D susceptibility in the Pakistani population. This case-control study includes 100 T1D patients (3-14 years), recruited randomly from the pediatric endocrinology department of Fatima Memorial Hospital, Lahore, Pakistan and 100 age-matched healthy controls were selected from different localities of the same population. The polymorphisms in PTPN22 (rs601, rs33996649, rs2488457), INS (rs80356664), NLRP3 (rs10754558, rs35829419), and ICAM-1 (rs1799969, rs5498) genes were genotyped by Sanger sequencing. The genotypic and allelic frequencies, haplotypes, and linkage disequilibrium were computed using the genetic toolset PLINK to investigate their relationship to T1D. The results indicate that the occurrence of the GT genotype of the rs33996649 variant is significantly higher in children with T1D compared to a control group of healthy individuals (P = 0.001, OR: 2.0, 95% CI = 0.15-0.45). Furthermore, the CT genotype of rs2488457 was notably associated with T1D patients (P = 0.007, OR: 2.8, 95% CI = 0.56-0.67). The CG genotype of rs80356664 showed a slight association with T1D (P = 0.03, OR: 1.9, 95% CI = 0.35-0.59). The prevalence of the AT genotype of rs10754558 showed a strong association with T1D (P = 0.005, OR: 3.4, 95% CI = 0.45-0.69). The TG genotype of rs5498 was also strongly associated with T1D (P = 0.009, OR: 2.8, 95% CI = 0.75-0.89). The present study provides evidence that SNPs in the PTPN22, INS, NLRP3, and ICAM-1 genes are associated with the development of T1D. Further research is needed to explore their potential use in genetic screening and personalized medication.

Concurrent genotyping and expression of NLRP3 inflammasome in pityriasis versicolor patient's skin lesions.

The goal of this study is to investigate the impact of the rs35829419 SNP on the serum level of NLRP3, and to assess the relationship between NLRP3 and its SNP and vulnerability to Pityriasis versicolor. Pityriasis versicolor (PV) is one of the most frequent skin conditions linked to skin pigmentation changes. Malassezia plays a key role in the pathogenesis of PV. A case-control study, 50 patients with pityriasis versicolor and 44 healthy controls. Real-time PCR was used to genotype NLRP3 (rs35829419) and ELISA assay of NLRP3 levels in tissue samples. There was a significantly higher median NLPR3 levels in PV patients than controls. A significant predominance of A allele of Q 705K was in patients than controls. The risk of having the disease in the presence of A allele is nearly 10 times than having C allele. In PV patients, there was a significant relationship between NLPR3 levels and Q 705K genotypes with higher NLPR3 levels in AA genotype. A potential correlation between PV and the Q705K polymorphism, pointing to evidence of NLRP3 alteration in PV patients. The NLRP3 inflammasome may be an appropriate therapeutic target for Malassezia-associated skin disorders.

The effects of NLRP3 rs10754558 and rs4612666 polymorphisms on preeclampsia susceptibility, onset, and severity: a case-control study and in silico analysis.

Preeclampsia (PE) is one of the serious complications of pregnancy and its exact etiology is unknown. Inflammasomes are multiportion complexes whose relation with PE has been described. Evidence showed the effect of NLRP3 inflammasome in PE pathogenesis. In the current study, we investigated the possible impacts of NLRP3 polymorphisms on PE. A total of 252 PE and 258 control pregnant women were selected for the study. The PCR-RFLP method was employed to genotype rs10754558 and rs4612666 polymorphisms. The RNAsnp and SpliceAid 2 software were used for in silico analysis. There was no relationship between NLRP3 polymorphisms and PE. In comparison to control women, the NLRP3 rs10754558 could increase the risk of severe PE in codominant and dominant models (OR=1.89, 95% CI=1.19-3.01, P=0.012, OR=1.95, 95% CI=1.24-3.06, P=0.0037, respectively). The findings of the in silico analysis revealed the effects of rs10754558 C to G and rs4612666 C to T substitutions on protein binding sites and rs10754558 C to G substitution on secondary RNA structure. These findings could confirm the finding those studies reported the impacts of these variants on various diseases. In conclusion, the NLRP3 rs10754558 variant was associated with an increased risk of EOPE and severe PE.

Impact of NLRP3 gene polymorphisms (rs10754558 and rs10733113) on HPV infection and cervical cancer in southern Chinese population

ObjectiveMutations in the NLRP3gene have previously been linked to certain forms of cancer, but there have not been any specific studies examining the association between NLRP3 polymorphisms and cervical cancer (CC). This study was therefore designed to investigate the effect of NLRP3 gene polymorphisms on HPV infection and cervical cancer in southern Chinese population.MethodsMultiplex PCR and next-generation sequencing approaches were used to assess the NLRP3 rs10754558 and rs10733113 polymorphisms in 404 cervical lesion patients, including 227 diagnosed with CC and 177 diagnosed with cervical intraepithelial neoplasia(CIN), with 419 healthy female controls being included for comparison. Correlations between the rs10754558 and rs10733113 genotypes and alleles in these patients and CC and CIN were then analyzed.ResultsNo correlations were found between NLRP3 rs10754558 and rs10733113 and human papillomavirus(HPV) infection status. Relative to the healthy control group, the NLRP3 rs10754558 GG genotype, CG + GG genotype, and G allele frequencies were significantly increased among patients with cervical lesions (CC and CIN) (OR = 1.815,P = 0.013;OR = 1.383, P = 0.026; OR = 1.284, P = 0.014,respectively), whereas no such differences were observed for rs10733113. A higher cervical lesion risk was detected for patients over the age of 45 exhibiting the rs10754558 GG genotype (OR = 1.848, P = 0.040). Additionally, the risk of CC was elevated in patients with the rs10754558 GG genotype or the G allele relative to patients with the CC genotype or the C allele(OR = 1.830, P = 0.029; OR = 1.281, P = 0.039). The rs10733113 genotypes or alleles were not significantly associated with CC risk (P > 0.05). No association between rs10754558 and rs10733113 genotypes and CC patient clinicopathological features were observed (P > 0.05). Serum NLRP3, IL-1β, and IL-18 levels were significantly elevated in CC patients relative to healthy controls(P < 0.05). Relative to the CC genotype, CC patients harboring the rs10754558 GG genotype exhibited significantly elevated IL-1β and IL-18 levels(P < 0.05).ConclusionThe rs10754558 polymorphism in the NLRP3 gene may contribute to an elevated risk of CC, although it is not significantly correlated with HPV infection and CC progression.

The role of NLRP3 and CARD8 polymorphisms in the risk of rheumatoid arthritis: A meta-analysis of genetic association studies.

To investigate the potential associations between rheumatoid arthritis (RA) and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) rs35829419, rs10754558, s4612666, and caspase recruitment domain family member 8 (CARD8) rs2043211 polymorphisms. Relevant papers were searched for in MEDLINE, Embase, and Web of Science. Allele contrast, recessive, dominant, and homozygote contrast models were used to investigate the relationship between the NLRP3 rs35829419, rs10754558, and s4612666, and CARD8 rs2043211 polymorphisms and RA. This review was registered with PROSPERO (CRD42023451231). The meta-analysis included 11 comparative studies comprising 3789 patients with RA and 3956 controls. No significant association was found between NLRP3 rs35829419 C allele and RA in Europeans, Arabs, or Latinos. The NLRP3 rs10754558 G allele was not associated with RA in the Asian or Arab populations. However, a single study in Latin America discovered a link between RA and the NLRP3 rs10754558 G allele. The NLRP3 rs4612666 T allele was not associated with RA, according to the meta-analysis. When ethnicity was stratified, there was no association between the NLRP3 rs4612666 T allele and RA, except for a single study that found an association among Arabs. The CARD8 rs2043211 T allele did not seem to be associated with RA. According to an ethnic stratification study, the CARD8 rs2043211 T allele did not appear to be associated with RA in Europeans, Arabs, or Latinos. The meta-analysis indicated that the NLRP3 rs35829419, rs10754558, and s4612666 polymorphisms, as well as the CARD8 rs2043211 polymorphism, were not linked to RA susceptibility.

The NLRP3 inflammasome rs35829419 C>A polymorphism is associated with type 2 diabetes mellitus in Saudi Arabia.

To investigate the frequency of NLRP3 gene rs35829419C>A single-nucleotide polymorphism (SNP) in a Saudi Arabian population from Jazan (Southwest Saudi Arabia) and test its potential association with type 2 diabetes mellitus (T2DM). This case-control study included 546 volunteers (271 patients with T2DM and 275 healthy controls) recruited from outpatient clinics at Jazan University Hospital and King Fahad Central Hospital in Jazan, Saudi Arabia, between December 2021 and July 2022. Genomic DNA was extracted from all samples and genotyped for the NLRP3 rs35829419C>A SNP using TaqMan technology. The association between the NLRP3 rs35829419 polymorphism and T2DM was examined using logistic regression analysis. Overall genotype distributions were 90.5% (CC), 9.3% (CA), and 0.2% (AA). The heterozygous CA genotype was more frequent in T2DM group (12.2%) compared to the control group (6.5%) and logistic regression analysis showed a statically significant association with T2DM risk under codominant (CA versus CC; odds ratio [OR]=1.99; 95% confidence interval [CI]= [1.11-3.61]; p=0.0270), and dominant (CA+AA versus CC; OR=2.05; CI=[1.16-3.75]; p=0.019) models of inheritance. This study revealed the frequency of NLRP3 rs35829419C>A polymorphism in our population and showed a direct correlation between having the minor allele for A and having a higher risk of developing T2DM. This study highlights the significance of NLRP3 rs35829419C>A polymorphism in the pathophysiology of T2DM.

Inflammasome genes polymorphisms are associated with progression to mechanical ventilation and death in a cohort of hospitalized COVID-19 patients in a reference hospital in Rio de Janeiro, Brazil

COVID-19 has a broad spectrum of clinical manifestations. We assessed the impact of single nucleotide polymorphisms (SNPs) of inflammasome genesas risk factors for progression toCOVID-19 critical outcomes, such as mechanical ventilation support (MVS) or death.The study included 451 hospitalized individuals followed up at the INI/FIOCRUZ, Rio de Janeiro, Brazil, from 06/2020 to 03/2021. SNPs genotyping was determined by Real-Time PCR. We analyzed risk factors for progression to MVS (n = 174[38.6 %]) or death (n = 175[38.8 %])as a result of COVID-19 by Cox proportional hazardmodels.Slower progression toMVSwas associated with allele G (aHR = 0.66;P = 0.005) or the genotype G/G (aHR = 0.391;P = 0.006) in the NLRP3 rs10754558 or the allele G (aHR = 0.309;P = 0.004) in the IL1βrs1143634, while C allele in the NLRP3 rs4612666 (aHR = 2.342;P = 0.006) or in the rs10754558 (aHR = 2.957;P = 0.005) were associated with faster progression to death. Slower progression to death was associated to allele G (aHR = 0.563;P = 0.006) or the genotype A/G (aHR = 0.537;P = 0.005) in the CARD8 rs6509365; the genotype A/C in the IFI16 rs1101996 (aHR = 0.569;P = 0.011); the genotype T/T (aHR = 0.394;P = 0.004) or allele T (aHR = 0.68;P = 0.006) in the NLRP3 rs4612666, and the genotype G/G (aHR = 0.326;P = 0.005) or allele G (aHR = 0,68;P = 0.014) in the NLRP3 rs10754558. Our results suggest that inflammasome genetic variations might influence the critical clinical course of COVID-19.

Posttraumatic Osteomyelitis Risks Associated with NLRP3 Gene Polymorphisms in the Chinese Population

The purpose of this case-control study was to examine possible links between NLRP3 gene polymorphisms and the risk of developing posttraumatic osteomyelitis (PTOM) in the Chinese population. A total of 306 patients with PTOM and 368 normal controls were genotyped for NLRP3 (rs35829419, rs10754558, rs7525979, rs4612666), ELP2 (rs1785929, rs1789547, rs1785928, rs12185396, rs681757, rs8299, rs2032206, rs559289), STAT3 (rs4796793, rs744166, rs1026916, rs2293152, rs1053004), CASP1 (rs501192, rs580253, rs556205, rs530537), NFKBIA (rs696), NFKB1 (rs4648068), CARD8 (rs204321), and CD14 (rs2569190) using the genotyping technique SNaPshot. The genotype distributions of NLRP3 gene rs10754558 (p = 0.047) and rs7525979 (p = 0.048) significantly differed between the patients and the healthy controls. Additionally, heterozygous models indicated a significant association between NLRP3 rs10754558 and the likelihood of developing PTOM (OR = 1.600, p = 0.039), as did recessive and homozygous models of NLRP3 rs7525979 (OR = 0.248, p = 0.019 and 0.239, p = 0.016, respectively). Collectively, our findings suggest that, in the Chinese population, the risk of developing PTOM was increased by the association between NLRP3 rs10754558 and rs7525979. Therefore, our findings may provide novel insights and guidance in the prevention and development of PTOM.

Can Polymorphisms in NLRP3 Inflammasome Complex Be Associated with Postmenopausal Osteoporosis Severity?

We genotyped 196 postmenopausal OP patients and 103 healthy controls using SNV-specific Taqman® probes. Data and statistical analyses were performed using the SNPstats and GraphPad Prism 8 software. We showed an association between NLRP3 rs35829419 CA genotype and lower bone mineral density (BMD) mean at the lumbar spine (p = 0.001); we also observed an association between IL-1β rs16944 AA genotype and higher BMD mean at the total hip (p = 0.009). The IL-1β rs16944 GG was associated with lower alkaline phosphatase levels (ALP) (p = 0.009), and the IL-18 rs1946519 AA was associated with lower vitamin D levels (p = 0.018). Additionally, OP patients presented deficient vitamin D and parathyroid hormone (PTH). The NLRP3 inflammasome complex SNVs were associated with OP severity, possibly indicating these genes' participation in bone metabolism and its dysregulation.

Inflammasome genetic variants are associated with tuberculosis, HIV-1 infection, and TB/HIV-immune reconstitution inflammatory syndrome outcomes.

BackgroundTuberculosis (TB) and AIDS are the leading causes of infectious diseases death worldwide. Here, we investigated the relationship between from single nucleotide polymorphisms (SNPs) of the NLRP3, CARD8, AIM2, CASP-1, IFI16, and IL-1β inflammasome genes, as well as the profiles of secreted proinflammatory cytokines (e.g., IL-1β, IL-18, IL-33, and IL-6) with the TB clinical profiles, TB-HIV coinfection, and IRIS onset.MethodsThe individuals were divided into four groups: TB-HIV group (n=88; 11 of them with IRIS), HIV-1 group (n=20), TB group (n=24) and healthy volunteers (HC) group (n=10), and were followed up at INI/FIOCRUZ and HGNI (Rio de Janeiro/Brazil) from 2006 to 2016. Real-time PCR was used to determine the genotypes of the Single Nucleotide Polymorphism (SNPs), and ELISA was used to measure the plasma cytokine levels. Unconditional logistic regression models were used to perform risk estimations.ResultsA higher risk for extrapulmonary TB was associated with the TT genotype (aOR=6.76; P=0.026) in the NLRP3 rs4612666 Single Nucleotide Polymorphism (SNP) and the C-C-T-G-C haplotype (aOR=4.99; P= 0.017) in the NLRP3 variants. This same Single Nucleotide Polymorphism (SNP) was associated with lower risk against extrapulmonary TB when the carrier allele C (aOR=0.15; P=0.021) was present. Among those with HIV-1 infections, a higher risk for TB onset was associated with the GA genotype (aOR=5.5; P=0.044) in the IL1-β rs1143634 Single Nucleotide Polymorphism (SNP). In contrast, lower risk against TB onset was associated with the A-G haplotype (aOR=0.17; P= 0.026) in the CARD8 variants. Higher IL-6 and IL-33 levels were observed in individuals with TB. A higher risk for IRIS onset was associated with CD8 counts ≤ 500 cells/mm3 (aOR=12.32; P=0.010), the presence of extrapulmonary TB (aOR=6.6; P=0.038), and the CT genotype (aOR=61.06; P=0.026) or carrier allele T (aOR=61.06; P=0.026) in the AIM2 rs2276405 Single Nucleotide Polymorphism (SNP), whereas lower risk against IRIS onset was associated with the AT genotype (aOR=0.02; P=0.033) or carrier allele T (aOR=0.02; P=0.029) in the CARD8 rs2043211 Single Nucleotide Polymorphism (SNP) and the T-G haplotype (aOR=0.07; P= 0.033) in the CARD8 variants. No other significant associations were observed.ConclusionsOur results depict the involvement of genetic polymorphisms of crucial innate immunity genes and proinflammatory cytokines in the clinical outcomes related to TB-HIV coinfection.

Association of NLRP1 (rs878329) and NLRP3 (rs10754558) genes polymorphism in psoriasis vulgaris patients with dyslipidemia

Introduction and aimNLRP inflammasome is intracellular sensors and not yet fully studied in psoriasis vulgaris. The aim was to investigate the association of NLRP1 (rs878329) and NLRP3 (rs10754558) genes polymorphism and psoriasis vulgaris, and their relations with the clinical and lipid profiles in psoriatic patients. Material and methodsThis study was involved 64 patients with psoriasis vulgaris and 64 healthy control group. Blood sample was taken for lipid profiles and genotypes NLRP1 and NLRP3 using single-nucleotide polymorphism (SNP) assay. ResultsTotal cholesterol and LDL-c were significantly increased in psoriatic patients compared to controls and their significantly correlation with PASI score (r = −0.296, −0.309 respectively; P < 0.05). On analyzing NLRP1 genotypes CG and GG; and the allele G showed significantly higher frequency in psoriatic patients with 4, 9 and 3 times increase in the risk of developing psoriasis vulgaris respectively; and was significantly associated with dyslipidemia. While on analyzing NLRP3 genotypes GC and CC; and the allele C showed significantly higher frequency in psoriatic patients with 6, 9 and 3 times increase in the risk of developing psoriasis vulgaris respectively. The genotype CC was significantly associated with family history of psoriasis (46.7%), site of affection distribution in extremities and axial (P = 0.015), and with severe form of psoriasis (40.0%) than genotypes GG and GC. However, NLRP3 genotypes was non-significantly associated with dyslipidemia. ConclusionsNLRP1 and NLRP3 genotypes polymorphism associated with more susceptibility to psoriasis vulgaris associated with dyslipidemia. NLRP3 genotypes polymorphism could assess severity and a pivotal therapeutic target in psoriasis vulgaris pathogenesis.

Innate Immune Responses in Pediatric Patients with Gastritis-A Trademark of Infection or Chronic Inflammation?

The aim of this study was to define the relationship between several environmental, laboratory, and genetic factors, i.e., TLR2 and NLRP3 polymorphisms, and Helicobacter pylori (H. pylori) infection in children, by comparing three different groups of pediatric subjects: H. pylori-induced gastritis, non-H. pylori gastritis, and healthy controls. Our final study sample included 269 children, which were divided into three groups according to the histopathological exam: group 1 with 51 children with H. pylori-induced gastritis, group 2 with 103 children with H. pylori-negative gastritis, and group 3 (control group) with 115 children without any histopathological changes. All children underwent a thorough anamnesis, clinical exam, laboratory tests, and upper digestive endoscopy with gastric biopsy for rapid urease test, histopathological exam, and genetic analysis of TLR2 rs3804099, TLR2 rs3804100, and NLRP3 rs10754558 gene polymorphisms. We noticed a significant association between living conditions and the type of gastritis (p < 0.0001). Both rapid urease and serological tests were significantly associated with the presence of H. pylori (p < 0.0001). The CT variant genotype of TLR2 rs380499 was significantly associated with neutrophil count (p = 0.0325). We noticed a significant association between the CC variant genotype of NLRP3 rs10754558 and leucocytes, neutrophils, eosinophils, as well as ALT (p = 0.0185, p = 0.0379, p = 0.0483, p = 0.0356). Based on these findings, we state that poor living conditions and rural areas represent risk factors for H. pylori infection. The rapid urease test is a reliable diagnostic tool for this infection. CT and TT carriers of TLR2 rs3804099, as well as CC carriers of NLRP3 rs10754558, might display a more severe degree of systemic inflammation.

In COVID-19, NLRP3 inflammasome genetic variants are associated with critical disease and these effects are partly mediated by the sickness symptom complex: a nomothetic network approach.

In coronavirus disease (COVID-19), the nucleotide-binding domain, leucine-rich repeat and pyrin domain-containing protein 3 (NLRP3) inflammasome is activated in response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Acute infections are accompanied by a sickness symptom complex (SSC) which is highly conserved and protects against infections and hyperinflammation. The aim of this study is to delineate the associations of COVID-19, SSC and NLPR3 rs10157379 T > C and NLPR3 rs10754558 C > G variants; and the protective role of SSC in SARS-CoV-2 infection. We recruited COVID-19 patients, 308 with critical, 63 with moderate and 157 with mild disease. Increased SSC protects against SARS, critical disease, and death due to COVID-19. Increasing age, male sex and rs10754558 CG significantly reduce SSC protection. The rs10157379 CT and rs10754558 GG genotypes are positively associated with SARS. Partial Least Squares analysis shows that a) 41.8% of the variance in critical COVID-19 symptoms is explained by SSC and oxygen saturation (inversely associated), inflammation, chest computed tomography abnormalities, increased body mass index, SARS and age (positively associated); and b) the effects of the NLRP3 rs10157379 and rs10754558 variants on critical COVID-19 are mediated via SSC (protective) and SARS (detrimental). SSC includes anosmia and dysgeusia, and maybe gastrointestinal symptoms. In conclusion, intersections among the rs10754558 variant, age, and sex increase risk towards critical COVID-19 by attenuating SSC. NLRP3 variants play an important role in SARS, and severe and critical COVID-19 especially in elderly male individuals with reduced SSC and with increased BMI, hypertension, and diabetes type 2.

Associations between inflammasome‐related gene NLRP3 Polymorphisms (rs10754558 and rs35829419) and risk of bladder cancer in a Chinese population

BackgroundNLRP3 inflammasome as a component of immune system has been found related to several cancers, but no study has assessed NLRP3 polymorphisms on risk of bladder cancer (BC). We aim to investigate whether NLRP3 polymorphisms are associated with the risk and clinical features of bladder cancer (BC) in a Chinese population.MethodsGenotype frequency of two commonly studied NLRP3 SNPs (rs10754558 and rs35829419) was examined in 154 patients with BC and the 308 healthy controls. NLRP3 gene polymorphisms were genotyped by polymerase chain reaction‐restriction fragment length polymorphism method.ResultsThe distribution frequencies of GG, AG+GG, GG, and G allele in NLRP3 (rs10754558) genotypes were significantly different between case and control group (OR = 2.296, P = .022; OR = 1.598, P = .020; OR = 1.998, P = .049; OR = 1.557, P = .006), but no statistical difference existed for rs35829419. Among smokers and alcohol drinkers, for rs10754558, individuals with AG, GG, and GG+AG genotypes had a higher BC risk compared with individuals with AA; for rs35829419, individuals with variant genotypes (AG and GG+AG) had a stronger risk of developing BC compared with individuals with AA (all P < .05). In stratified analyses of tumor size and tumor node metastasis, AG or GG genotypes of rs10754558 and rs35829419 SNPs were associated with BC risk (both P < .05).ConclusionNLRP3 polymorphisms (rs10754558 and rs35829419) were related to BC risk and tumor size and lymph node metastasis, especially among smokers and alcohol drinkers.

Associations of NLRP3 and CARD8 gene polymorphisms with alcohol dependence and commonly related psychiatric disorders: a preliminary study.

We investigated two functional polymorphisms in NLRP3 inflammasome genes (NLRP3 rs35829419 and CARD8 rs2043211) and their association with alcohol dependence and related anxiety, depression, obsession-compulsion, or aggression in 88 hospitalised alcohol-dependent patients, 99 abstinent alcohol-dependent participants, and 94 controls, all male Caucasian. Alcohol dependence-related psychiatric disorders were assessed with the Zung Depression and Anxiety scale, Buss-Durkee Hostility Inventory, Alcohol Use Disorders Identification Test, Brief Social Phobia Scale, Obsessive Compulsive Drinking Scale, and Yale-Brown Obsessive-Compulsive Scale. For genotyping we used the allele-specific quantitative polymerase chain reaction-based methods. The three groups differed significantly in CARD8 rs2043211 distribution (P=0.049; chi-squared=9.557; df=4). The NLPR3 rs35829419 polymorphism was not significantly associated with alcohol dependence. In hospitalised alcohol-dependent patients the investigated polymorphisms were not associated with scores indicating alcohol consumption or comorbid symptoms. In abstinent alcohol-dependent subjects homozygotes for the polymorphic CARD8 allele presented with the highest scores on the Zung Anxiety Scale (p=0.048; df=2; F=3.140). Among controls, CARD8 genotype was associated with high scores on the Obsessive Compulsive Drinking Scale (P=0.027; df=2; F=3.744). In conclusion, our results reveal that CARD8 rs2043211 may play some role in susceptibility to alcohol dependence, expression of anxiety symptoms in abstinent alcohol-dependent subjects, and in obsessive compulsive drinking in healthy controls. However, further studies with larger cohorts are required to confirm these preliminary findings.

Genetic Polymorphisms, Gene–Gene Interactions and Neurologic Sequelae at Two Years Follow-Up in Newborns with Hypoxic-Ischemic Encephalopathy Treated with Hypothermia

Inflammation and oxidative stress after hypoxic-ischemic brain injury may be modified by genetic variability in addition to therapeutic hypothermia. The aim of our study was to evaluate the association between the polymorphisms in genes of antioxidant and inflammatory pathways in newborns treated with therapeutic hypothermia and the development of epilepsy or CP at two years follow-up. The DNA of 55 subjects was isolated from buccal swabs. Genotyping using competitive allele-specific PCR was performed for polymorphisms in antioxidant (SOD2 rs4880, CAT rs1001179, GPX1 rs1050450) and inflammatory (NLRP3 rs35829419, CARD8 rs2043211, IL1B rs1143623, IL1B rs16944, IL1B rs10716 76, TNF rs1800629) pathways. Polymorphic CARD8 rs2043211 T allele was less frequent in patients with epilepsy, but the association was not statistically significant. The interaction between CARD8 rs2043211 and IL1B rs16944 was associated with epilepsy after HIE: CARD8 rs2043211 was associated with lower epilepsy risk, but only in carriers of two normal IL1B rs16944 alleles (ORadj = 0.03 95% CI = 0.00–0.55; padj = 0.019). Additionally, IL1B rs16944 was associated with higher epilepsy risk only in carriers of at least one polymorphic CARD8 rs2043211 (ORadj = 13.33 95% CI = 1.07–166.37; padj = 0.044). Our results suggest that gene–gene interaction in inflammation pathways might contribute to the severity of brain injury in newborns with HIE treated with therapeutic hypothermia.

The Expression of Allele Changes in NLRP3 (rs35829419) and IL-1β (+3954) Gene Polymorphisms in Periodontitis and Coronary Artery Disease.

Background: Inflammasomes have been shown to play a pivotal role in periodontal disease pathogenesis. However, their role in periodontitis subjects with coronary heart disease remains unclear. This study aimed to obtain the expression of NLRP3 (rs35829419) and IL-1β (+3954) gene polymorphisms in the subgingival plaque and blood samples of generalized periodontitis (GP) subjects with and without coronary heart disease (CHD). Methods: A total of 70 subjects were grouped into two; GP and GP with CHD. Demographic variables and periodontal and cardiac parameters were recorded from both the groups. Subgingival plaque and blood samples were obtained from both the groups and were further subjected to the identification of NLRP3 (rs35829419) and IL-1β (+3954) expression and allele change using a conventional polymerase chain reaction (PCR) and gene sequencing (Sanger’s method). Results: Amongst the demographic variables, age and monthly income were statistically significant between the two groups. Plaque index (PI), clinical attachment level (CAL), high-density lipoprotein (HDL), and low density-lipoprotein (LDL) exhibited statistically significant levels between the two groups. The NLRP3 (rs35829419) and IL-1β (+3954) genes showed a statistically significant association with allele change (frequency) among the groups. The general comparison of all the parameters with the allele change of NLRP3 (rs35829419) and IL-1β (+3954) in the subgingival plaque and blood samples showed statistically significant associations among the two groups. Conclusion: The present study highlighted an allele change in IL-1β (+3954) gene polymorphisms which may play an important role in the pathogenesis of periodontitis and coronary heart disease.

NLRP3 gene polymorphisms and expression in rheumatoid arthritis.

The present study aimed to investigate the association between the single-nucleotide polymorphisms (SNPs) rs4612666 and rs10754558 in the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) gene and the susceptibility to rheumatoid arthritis (RA) in a Han Chinese population. mRNA expression of NLRP3, apoptosis-associated speck-like protein (ASC), and caspase-1 were determined in peripheral blood mononuclear cells (PBMCs) and neutrophils using reverse-transcription quantitative PCR. The results demonstrated that the C allele at rs4612666 locus and the G allele at rs10754558 locus were associated with significantly increased risk of RA. A statistical significance was also revealed in the dominant model (CC+CT vs. TT: OR=1.549; 95% CI=1.120-2.144; and GG + GC vs. CC: OR=2.000; 95% CI=1.529-2.616; P<0.05). Additionally, the mRNA expression of NLRP3, ASC and caspase-1 in PBMCs and neutrophils derived from patients with RA were significantly upregulated compared with the controls. Furthermore, the mRNA levels of NLRP3, ASC and caspase-1 in PBMCs and neutrophils from patients with active RA were notably increased compared with patients in remission. NLRP3 expression was positively correlated with the levels of C-reaction protein, erythrocyte sedimentation rate and disease activity score of 28 joint counts. Overall, the current study indicated that the NLRP3 rs4612666 and rs10754558 loci were associated with susceptibility to RA. In addition, the results of the present study demonstrated that the high expression of NLRP3 could serve a critical role in the pathogenesis of RA.

Evaluation of NLRP3 (rs10754558) and PTPN22 (1858C/T) (rs2476601) Functional Polymorphisms in Psoriasis Susceptibility in Egypt.

BackgroundPsoriasis is a complex autoimmune multifactorial disease induced by interaction of environmental and genetic factors. This research aimed to clarify the association of NLRP3 (rs10754558) and PTPN22 (1858C/T) (rs2476601) polymorphisms with susceptibility to psoriasis.MethodsThis case–control study involved 150 patients diagnosed with psoriasis and 100 age- and gender-matched apparently healthy individuals. NLRP3 (rs10754558) polymorphism was done by real time PCR and PTPN22 1858C/T (rs2476601) genotype was identified by tetra-primer amplification refractory mutation system-polymerase chain reaction (PCR) method.ResultsThe genotypes distribution of NLRP3 (rs10754558) were significantly associated with psoriasis (p<0.0001). Whereas for PTPN22 (1858C/T) (rs2476601), no significance was found (p=0.09). NLRP3 (rs10754558) GC genotype revealed a significant association with psoriasis (p<0.0001), mainly among male (p=0.004) patients with mild psoriasis (p=0.001) and affected extremities (p=0.0001).ConclusionWe can conclude that the NLRP3 (rs10754558) GC genotype may play a role in psoriasis susceptibility among male Egyptian populations with affected extremities. Future studies must evaluate its role in the prevention or the treatment of psoriasis.

Role of NLRP3rs10754558 and NOS3rs1799983 genetic polymorphisms in smoking and nonsmoking COPD patients

Chronic Obstructive Pulmonary Disease (COPD) is a chronic inflammatory disease leading to structural abnormalities in the airways. Mortality and disability in COPD cases are high, causing an intense economic burden. This study aims to investigate the relationship between NLRP3 rs10754558 and NOS3rs1799983 polymorphisms and the risk of COPD. This work was carried out on 152 subjects classified into Group I, with 38 COPD patients who are smokers, Group II 38 nonsmoker COPD patients, Group III 38 healthy smokers, and Group IV with 38 healthy nonsmokers. Genotyping of NLRP3rs10754558C/G and NOS3rs1799983G/T polymorphisms was assayed by real-time PCR. For NLRP3rs10754558 polymorphism, significantly higher frequencies of G/G genotype versus C/C were evident in COPD patients more than controls (p ≤ 0.001). Also, G allele can increase the risk of COPD by (OR) 95% CI [2.498 (1.521–4.101)]. Higher frequencies of mutant G/T and T/T genotypes of NOS3 rs1799983 versus G/G in COPD patients (48.7% and 17.1%) were more than the values evident in controls (p = 0.004 and 0.005). T allele can also increase the risk of COPD by (OR) 95% CI [2.457 (1.491–4.049)]. Conceivable LD was evident between both polymorphisms in COPD patients and controls. No significant difference between the severity of COPD was detected by the GOLD staging and the studied polymorphisms variants in the COPD group (p = 0.441 and 0.83). Coding polymorphisms in NLRP3 and NOS3 can be associated with the hazard of COPD and the probability of cigarette smokers suffering the studied polymorphisms to develop COPD.