rs3804100、rs3804099及rs2295080基因多态性与黑龙江省2型糖尿病患者并发肺结核关系的研究

目的探究Toll样受体2(Toll-like receptor 2,TLR2)rs3804100、rs3804099位点和哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)rs2295080位点基因多态性与2型糖尿病并发肺结核的关系。方法选择2017年1-9月黑龙江省传染病防治院收治的300例2型糖尿病并发肺结核患者作为观察组,以及同时期在哈尔滨医科大学附属第四医院内分泌科就诊的300例2型糖尿病患者作为对照组。所有患者收集血液提取DNA,用PCR技术对TLR2的rs3804100、rs3804099位点及mTOR的rs2295080位点进行基因多态性检测,并对这3个基因位点多态性与2型糖尿病并发肺结核的关系进行单因素和logistic多因素分析。结果单因素分析结果显示,TLR2的rs3804100位点TT、TC、CC(T:胸腺嘧啶;C:胞嘧啶)基因型在观察组和对照组分布构成比分别为51.3%(154/300)、25.7%(77/300)、23.0%(69/300)和47.0%(141/300)、31.3%(94/300)、21.7%(65/300),差异无统计学意义(χ^2=2.382,P=0.304);TLR2的rs3804099位点TT、TC、CC基因型在观察组和对照组分布构成比分别为53.0%(159/300)、29.7%(89/300)、17.3%(52/300)和54.3%(163/300)、33.0%(99/300)、12.7%(38/300),差异无统计学意义(χ^2=2.759,P=0.252);mTOR的rs2295080位点TT、TG、GG(G:鸟嘌呤)基因型在观察组和对照组分布构成比分别为26.7%(80/300)、67.3%(202/300)、6.0%(18/300)和24.3%(73/300)、66.0%(198/300)、9.7%(29/300),差异无统计学意义(χ^2=2.935,P=0.231)。logistic多因素分析结果显示,TLR2的rs3804100位点TC、CC基因型的OR(95%CI)值分别为1.261(0.591~2.689)和1.284(0.542~3.042),P值分别为0.549和0.569;TLR2的rs3804099位点TC、CC基因型的OR(95%CI)值分别为0.752(0.461~1.227)和0.729(0.430~1.235),P值分别为0.254和0.240;mTOR的rs2295080位点TG、GG基因型的OR(95%CI)值分别为1.789(0.890~3.596)和1.603(0.839~3.063),P值分别为0.103和0.153。结论 TLR2基因rs3804100、rs3804099位点及mTOR的rs2295080位点多态性与黑龙江省2型糖尿病并发肺结核均无相关性。     

Liver involvement in ANCA-associated vasculitis

The aim of the study was to investigate the incidence, the clinical course and outcome of liver involvement and autoimmune hepatic diseases in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Liver function tests (LFT) (i.e. aspartate and alanine aminotransferase [AST, ALT], gamma-glutamyl transpeptidase [gamma-GT], alkaline phosphatase [ALP] and total bilirubin) were analysed at disease onset in therapy-naïve patients and during remission in patients with granulomatosis with polyangiitis (GPA, n?=?67), microscopic polyangiitis (MPA, n?=?28) and eosinophilic granulomatosis with polyangiitis (EGPA, n?=?14). Results were correlated to the Birmingham Vasculitis Activity Score version 3 (BVAS v.3). Also, serologic tests for other autoimmune hepatic diseases were performed in these patients. During the active state, LFT abnormalities could be detected in 54 AAV patients (49.4 %). ALT, gamma-GT and ALP were significantly higher in GPA patients compared to MPA or EGPA patients at disease onset (p?<?0.05). Increased values for gamma-GT in GPA patients correlated with the BVAS (p?<?0.01) and were associated with pulmonary involvement, pulmonary-renal syndrome and a longer time to remission. Increased LFT in GPA patients decreased subsequently towards normal levels after initiation of therapy (p?<?0.01). No case of severe liver involvement or autoimmune hepatic liver diseases was found in AAV patients. Liver involvement was mainly restricted to GPA patients, is associated with the disease activity and indicates a poorer outcome in patients with GPA. Progressive liver involvement or autoimmune hepatic diseases were not observed.     

Association of polymorphisms in SPARC and NLRP2 genes with rheumatoid arthritis in a Chinese Han population

Abstract

Objectives. To investigate the association of the polymorphisms in SPARC and NLRP2 with rheumatoid arthritis (RA) in a Chinese Han population.

Methods. Four single nucleotide polymorphisms (SNPs) covering SPARC and three SNPs covering NLRP2 were investigated in 624 Chinese Han RA patients and 1920 healthy controls.

Results. The A allele at SPARC rs3210714, SPARC rs11950384, NLRP2 rs2217659, and NLRP2 rs703468 were linked to reduced risk of RA (p = 0.0016, p = 0.0051, p < 0.0001, and p = 0.0033, respectively). Under the recessive model, the A/A genotype of rs3210714, rs11950384, rs2217659, and rs703468 were relevant with RA (p = 0.0071, p = 0.017, p < 0.0001 and p = 0.0066, respectively). Haplotype analysis identified the SPARC GGCG haplotype, AAAA haplotype were associated with the risk for RA (p < 0.0001 and p = 0.0015, respectively), while the risk of RA was lower for carriers of the GAAA haplotype (p < 0.0001), AACG haplotype (p < 0.0001), and the AGCG haplotype (p < 0.0001). The NLRP2 GG haplotype was a risk factor (p < 0.0001), while the GA haplotype and the AG haplotype were associated with lower risk of RA (p < 0.0001 and p = 0.0017, respectively). There was no significant difference between the RA patients and the controls in polymorphisms of rs7719521, rs1978707, and rs269913.

Conclusion. This study indicates that polymorphisms in SPARC and NLRP2 are related to RA susceptibility in a Chinese Han population.     

IRF5, but not TLR4, DEFEB1, or VDR,is associated with the risk of ulcerative colitis in a Han Chinese population

Abstract

Objective. IRF5, TLR4, DEFB1, and VDR genetic variations have been associated with ulcerative colitis (UC) in several European patient cohorts. As distinct genetic backgrounds may play a role in different ethnicities, we evaluated the effects of single-nucleotide polymorphisms (SNPs) in these genes and their interactions in UC patients of Han Chinese descent. Material and methods. DNA samples from 300 UC patients and 302 healthy control subjects from Peking Union Medical College Hospital were genotyped for 14 tag SNPs, which were selected based on haplotype analysis of IRF5, TLR4, DEFB1, and VDR. Multidimensionality reductions were used to explore gene–gene interactions. Results. The only observed association with UC was for IRF5. On an allelic level, SNP rs3807306 was associated with UC risk (p = 6.7 × 10^?3). On a genotypic level, the CC genotype of SNP rs3807306 (p = 0.03) was associated with protection from UC, and the AA genotype of SNP rs4728142 (p = 7.6 × 10^?3) was associated with a risk of UC. In the haplotype analysis, GGATT was highly correlated with UC risk (p-Value = 2.0 × 10^?4). No significant multilocus interactions were detected among these four genes. Conclusions. Our study confirmed the association of IRF5 with UC in Han Chinese patients. Han Chinese UC patients share part of their genetic susceptibility with Caucasian patients.     

The cancer risk according to three subtypes of ANCA-associated vasculitis: A propensity score-matched analysis of a nationwide study

ObjectiveIt remains unknown whether cancer risk differs among the three subtypes of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) and what the cancer risk factors are. We conducted a nationwide study in Korea to evaluate the risk of cancer in patients with AAV and to identify the risk factors for cancer.MethodsWe analyzed the Health Insurance Review and Assessment database of Korea and identified 1982 patients diagnosed with AAV between January 1, 2007 and December 31, 2017. The patients and controls with no history of AAV or cancer were matched 1:4 by propensity scores. The study outcome measure was incidence of cancer during 11 years of follow-up.ResultsPatients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and eosinophilic granulomatosis with polyangiitis (EGPA) numbered 684, 606, and 692, respectively. The overall incidence of cancer was higher among patients with AAV than in controls (HR 1.32, 95% CI 1.08–1.61). The risk of hematological malignancy, lung cancer, and bladder cancer in the GPA group, lung cancer in the MPA group, and hematological malignancy in the EGPA group were significantly higher than in controls (HR 7.39, 3.20, 4.20, 2.86, and 4.65, respectively). Age, male sex, GPA subtype, and cyclophosphamide use were significantly associated with cancer risk in patients with AAV.ConclusionOverall cancer incidence was increased in patients with AAV. Cancer risk was higher in patients with GPA than in those with MPA or EGPA. The use of cyclophosphamide was associated with an increased risk of cancer, while rituximab was not.     

Association of IL-1R2 genetic polymorphisms with the susceptibility of ankylosing spondylitis in Northern Chinese Han population

Objectives. Previous Genome-wide association studies (GWAS) have demonstrated Interleukin-1 receptor 2 (IL-1R2) was strongly associated with susceptibility to ankylosing spondylitis (AS). The aim of this study was to replicate the association of IL-1R2 single-nucleotide polymorphisms (SNPs) with AS in the northern Han Chinese.

Methods. A total of 490 AS patients and 580 matched healthy controls were enrolled in our study. Six tagSNPs in IL-1R2: rs4851526, rs4851527, rs2302589, rs2072476, rs2072472, and rs2310173 were selected and genotyped by Taqman SNP genotyping method. The differences of allele and genotype frequencies were analyzed by use of PLINK 1.07.

Results. Logistic regression analysis showed that one tagSNP rs2302589 in IL-1R2 was significantly associated with AS susceptibility (OR 0.77, 95% CI = 0.64–0.92, P = 0.005). However, no significant association was observed on the other tagSNPs for AS risk. The haplotype analysis further showed that the haplotype “GCGCGG” of IL-1R2 was also associated with the increased risk of AS (OR 1.362, P = 0.0207).

Conclusions. This is the first detection that the genetic variation rs2302589 in IL-1R2 gene was associated with AS in Northern Han Chinese. This result confirmed that IL-1R2 may be genetic biomarker for susceptibility to AS.     

Four cases of MPO-ANCA-positive vasculitis with otitis media, and review of the literature

Otitis media is one of the common organ injuries that appear during the course of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). We experienced four patients with myeloperoxidase (MPO)-ANCA-positive AAV with otitis media. All were elderly Japanese women. MPO-ANCA in our patients was reminiscent of microscopic polyangiitis (MPA), although chest computed tomography (CT) scans revealed characteristics of both granulomatosis with polyangiitis (GPA), showing bronchial lesions and nodule formation, and MPA, showing interstitial changes. Whether our cases should be classified as GPA or MPA is a matter of discussion. We detail their profiles, and review previous literature on MPO-ANCA-positive AAV with otitis media.     

Myeloperoxidase-ANCA-positive granulomatosis with polyangiitis is a distinct subset of ANCA-associated vasculitis: A retrospective analysis of 455 patients from a single center in China

Objective

Antineutrophil cytoplasmic antibody (ANCA) directed to proteinase 3 (PR3) used to be considered the serologic marker for granulomatosis with polyangiitis (GPA). However, patients with myeloperoxidase (MPO)-ANCA positive GPA have been increasingly reported. The aim of this study was to analyze the clinical and pathological characteristics and outcome of Chinese patients with MPO-ANCA positive GPA.

Laboratory Diagnosis of ANCA-Associated Vasculitis (AAV) Using a Combination of Immunofluorescence Test (IIFT) and Line Immunoassay (LIA): Single-Centre Report From India

IntroductionAnti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis (AAV) is a small vessel vasculitis with insufficient epidemiological estimates in India. We aimed to determine demographic, clinical features, and laboratory diagnosis of AAV patients presenting to a large tertiary care centre in India.Material and methods1289 patient samples were screened for ANCA by indirect immunofluorescence test (IIFT) and confirmation of ANCA target antigens was done by line immunoassay. Association between IIFT and LIA was determined in AAV.ResultsBy IIFT, ANCA was detected in 13.0% (168 out of 1289), of which 23.8% (40/168) were positive with P-ANCA pattern, 25.0% (42/168) were positive with C-ANCA and 47.6% (80/168) showed an atypical pattern. On evaluation with a line immunoassay, 6.7% (86/1289) were positive out of which 52.3% (45/86), 41.9% (36/86), 8.8% (6/86) were positive for anti-MPO, anti-PR3, and anti-GBM respectively. In eosinophilic granulomatosis with polyangiitis (EGPA) 87.5% (7/8), and microscopic polyangiitis (MPA/RLV) 91.3% (21/23), anti-MPO was the predominantly observed antibody. In granulomatosis with polyangiitis (GPA) anti-PR3 antibody was predominant in 87.5% (28/32) cases. Out of 168 IIF positive samples 8, 32, and 23 cases of EGPA, GPA, and MPA/RLV were observed respectively.ConclusionsThe primary aim of the study was to provide single-centre data to determine the laboratory diagnosis of AAV. A combination of IIFT and LIA was found to be an optimum testing strategy for the laboratory diagnosis of AAV.     

Empfehlungen zum Einsatz von Rituximab bei ANCA-assoziierten Vaskulitiden

Rituximab (Rtx) has been approved in Germany since April 2013 for treatment of granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). This therapy can be used in severe manifestations of these diseases and in relapses. It is administered as infusions of 375 mg rituximab per m² every 4 weeks after high dose intravenous prednisolone for 3 days and continued parallel to concomitant oral prednisolone therapy. Recommendations for the indications and use for antineutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV) are described in addition to previous publications on recommendations for rheumatoid arthritis.     

Association between PNPLA3 gene polymorphisms and risk of hepatitis B virus-related hepatocellular carcinoma in Han population in China:a case-control study

Background and aim: Several recent studies showed that the genetic polymorphisms in the PNPLA3 region (rs738408, rs738409, rs2294918, rs2294919 and rs2281135) were with related to various kinds of liver diseases. We analyzed the five single-nucleotide polymorphisms (SNPs) for major HBV outcomes in Han Chinese.

Methods: A total of 2410 samples were involved and peripheral blood samples were collected in this study. The SNPs in the PNPLA3 region were genotyped by using Matrix-assisted laser desorption/ionization time of flight mass spectrometry.

Results: Our study indicated the clear relationship between the PNPLA3 rs2294918, rs2294919 and HBV-related HCC after control for the effects of sex, drinking and smoking. Health subjects with the PNPLA3 rs2294919?TC genotype would have a 0.605 (95% CI: 0.413, 0.886; p?=?.010) times lower odds of having HCC, and those with the rs2294918 AG genotype would have a 1.872 (95% CI: 1.256, 2.792; p?=?.002) times higher odds of having HCC, whereas the values of sex, age, drinking and smoking were fixed. In addition, CA haplotype of the haplotype block of rs738409 and rs2281135 was also associated with HBV-related HCC.

Conclusions: Our study suggested that PNPLA3 loci (rs2294918, rs2294919) were associated with HBV-related HCC in Han Chinese.     

Classification of antineutrophil cytoplasmic autoantibody vasculitides: The role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis

Objective

To compare the usefulness of 3 currently used classification systems in predicting the outcomes of treatment resistance, disease relapse, end‐stage renal disease (ESRD), and death in patients with antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV).

Methods

Three classification systems were applied to 502 patients with biopsy‐proven AAV: 1) the Chapel Hill Consensus Conference (CHCC) definition with categories for granulomatosis with polyangiitis (GPA) (Wegener's), microscopic polyangiitis (MPA), and kidney‐limited disease; 2) the European Medicines Agency (EMA) system with categories for GPA and MPA; and 3) classification based on ANCA with specificity for myeloperoxidase (MPO ANCA) versus ANCA with specificity for proteinase 3 (PR3 ANCA). Outcomes included treatment resistance, relapse, ESRD, and death. Proportional hazards models were compared between systems using an information‐theoretic approach to rank models by predictive fit. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) and P values are reported.

Results

ANCA specificity was predictive of relapse, with PR3 ANCA–positive patients almost twice as likely to relapse as those with MPO ANCA (HR 1.89 [95% CI 1.33–2.69], P = 0.0004), and ANCA specificity had the best predictive model fit (model rank 1) compared to the CHCC and EMA systems. The CHCC and EMA systems did not predict relapse. By ANCA specificity, categories of GPA, MPA, and kidney‐limited disease did not distinguish differences in probability of relapse‐free survival. None of the systems predicted treatment resistance, ESRD, or death.

Conclusion

ANCA specificity independently predicts relapse among patients with AAV with renal disease. Classification and diagnostic systems that incorporate ANCA specificity, such as PR3 ANCA–positive MPA and MPO ANCA–positive MPA, provide a more useful tool than the clinical pathologic category alone for predicting relapse.

     

Patient-reported outcomes in ANCA-associated vasculitis. A comparison between Birmingham Vasculitis Activity Score and routine assessment of patient index data 3

The objective of this study was to determine health-related quality of life (HRQoL) in patients with ANCA-associated vasculitis (AAV) as measured by the “routine assessment of patient index data 3” (RAPID3) and whether RAPID3 is correlated with disease activity as determined by the Birmingham Vasculitis Activity Score (BVAS). Data from patients at an academic institution vasculitis clinic seen between Jan 2010 and Jan 2012 were collected using chart review. BVAS and RAPID3 scores were calculated at each patient visit. RAPID3 was compared between patients in remission (BVAS?=?0) and patients with active disease (BVAS?>?=1) at all visits for four consecutive visits, when data available, at least 3 months apart during the period mentioned. Robust generalized estimating equations (GEE) in linear regression models evaluated associations between the RAPID3 and BVAS over all available observations, adjusting for intra-subject correlations. Thirty-four patients were included in the study, 26 had granulomatosis with polyangiitis (GPA), five microscopic polyangiitis (MPA), and three eosinophilic granulomatosis with polyangiitis (EGPA). Patients at first visit had impaired HRQoL as measured by RAPID3 [6.8 (3.1–12.6)]. The median RAPID3 scores were higher in patients with active disease as compared to patients in remission (7.0 vs. 3.0, p?=?0.115; 8.8 vs. 1.0, p?=?0.011; 6.1 vs. 2.0, p?=?0.032; and 11.7 vs. 2.0, p?=?0.128 for visits 1, 2, 3, and 4, respectively). In longitudinal GEE models incorporating all observations there was a strong association between the RAPID3 (per 1 unit) and BVAS (per 1 unit) [β 0.21 (0.10, 0.32) p?<?0.001]. RAPID3 can be used to measure HRQoL in patients with AAV. RAPID3 correlated significantly with BVAS. RAPID3 can discriminate between disease states in AAV. This instrument may help document patient experience and add to clinical decisions.     

Polymorphisms in the Superoxide Dismutase-3 Gene Are Associated with Emphysema in COPD

ABSTRACT

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case–control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.     

A retrospective study on the outcomes of MPO-ANCA-associated vasculitis in dialysis-dependent patients

Objectives. This study investigated the clinical course of myeloperoxidase-antineutrophil cytoplasm autoantibody (MPO-ANCA)-associated vasculitis after starting dialysis.

Methods. A retrospective review was conducted of the clinical charts of dialysis-dependent patients with MPO-ANCA-associated vasculitis who attended one of 8 associated clinics over the past 21 years.

Results. Eighty-nine patients were included in the study; 88 had microscopic polyangiitis (MPA) and 1 had granulomatosis with polyangiitis. Of the 88 patients with MPA, 18 had renal-limited vasculitis. Twenty-one relapses occurred among 13 patients (frequency, 0.05 relapses/person-year; 95% confidence interval, 0.03–0.08). Mean time from start of dialysis to relapse was 65 ± 59 months. Cox multivariate analysis showed that pulmonary involvement was a predictor of relapse (hazard ratio [HR], 21.4) and mortality (HR, 4.60), and that patient age (HR, 1.10) and cyclophosphamide use (HR, 0.20) were significant predictors of mortality. Postdialysis 1- and 5-year survival rates were 83.0% and 65.6%, respectively; infection was the most frequent cause of death.

Conclusion. Pulmonary involvement was a predictor of relapse and mortality. Although relapse can occur long after the start of dialysis, incidence was low among dialysis-dependent patients. Prolonged maintenance immunosuppressive therapy might be limited to patients with pulmonary involvement in dialysis-dependent ANCA-associated vasculitis.     

A polymorphism in the ABCG1 promoter is functionally associated with coronary artery disease in a Chinese Han population

Objective

In this study, we examine the association of single nucleotide polymorphisms (SNPs) of the human ATP binding cassette transporter G1 (ABCG1) gene with atherosclerotic coronary artery disease (CAD) in a Chinese Han population.

Methods

1021 patients with CAD and 1013 unaffected control subjects were enrolled. PCR-based ligation detection reaction (PCR-LDR) method was used to genotype four SNPs of ABCG1, three (rs2234714, rs2234715 and rs57137919) in the promoter region and one (rs1044317) in the 3′-untranslated region (UTR).

Results

The human ABCG1 −367G>A polymorphism (rs57137919) showed a significantly decreased risk for CAD and myocardial infarction (MI) in a dominant model (adjusted OR = 0.73, p = 0.033 for CAD, and adjusted OR = 0.65, p = 0.014 for MI, respectively). The rs57137919 also showed an association with angiographic severity of CAD (multi-vessel vs. single-vessel CAD, adjusted OR = 0.40, p = 0.005). The findings were further supported by luciferase reporter assay, in which the polymorphism impaired reporter gene expression. The ABCG1 −768G>A polymorphism (rs2234714) showed an association with CAD in a recessive model (adjusted OR = 0.64, p = 0.015), but did not demonstrate a functional influence on reporter gene expression in the luciferase reporter assay.

Conclusions

The SNP rs57137919 in the ABCG1 promoter region is functionally associated with a reduced risk of CAD in a Chinese Han population.     

Associations of genetic polymorphisms of the vitamin D pathway with blood pressure in a Han Chinese population

Vitamin D deficiency can lead to high blood pressure. Polymorphisms in the vitamin D hydroxylase gene have been associated with serum vitamin D levels in some Western countries. The aim of this study was to investigate whether polymorphisms of hydroxylase genes in the vitamin D metabolic pathway contribute to hypertension by affecting serum vitamin D status in a Han Chinese population. We selected four single nucleotide polymorphisms (SNPs; rs1993116 and rs10741657 of CYP2R1; rs4809957 and rs6068816 of CYP24A1) for genotyping in 525 control subjects and 324 hypertensive patients, and detected vitamin D levels in blood in subsets of these groups. The results showed that rs1993116 and rs10741657 were associated with a reduced risk of hypertension. The odds ratios, 95% confidence intervals, and p values from the adjusted additive and dominant models were 0.788 (0.644–0.963, p = 0.02) and 0.719 (0.545–0.949, p = 0.02) for rs1993116 and 0.805 (0.66–0.983, p = 0.033) and 0.733 (0.556–0.966, p = 0.028) for rs10741657. A protective effect of CYP2R1 with regard to hypertension was also found in males and non-smokers. The TT genotypes of rs1993116 and rs10741657 were associated with significantly lower systolic blood pressure in treated hypertensive patients (both p = 0.002). No association with hypertension was found for the two SNPs of CYP24A1, and no difference in vitamin D level was found among the three genotypes of the four SNPs. Our results suggest that CYP2R1 polymorphisms are associated with a reduced risk of hypertension independent of the vitamin D level in the Han Chinese population.     

Single Nucleotide Polymorphisms of Interleukins and Toll-like Receptors and Neuroimaging Results in Newborns with Congenital HCMV Infection

Congenital cytomegalovirus infection (cCMV) is the most common intrauterine infection with central nervous system (CNS) involvement. There is limited data on the associations between Single Nucleotide Polymorphisms (SNPs) in genes involving the first-line defense mechanism and the risk of CNS damage during cCMV. We investigated the associations between neuroimaging findings and SNPs in genes encoding the following cytokines and cytokine receptors in 92 infants with cCMV: interleukins (IL1B rs16944, IL12B rs3212227, IL28B rs12979860), C-C motif chemokine ligand 2 (CCL2 rs1024611), dendritic cell-specific intercellular adhesion grabbing non-integrin (DC-SIGN rs735240), Toll-like receptors (TLR2 rs5743708, TLR4 rs4986791, TLR9 rs352140). The SNP of IL1B rs16944 (G/A) was associated with a reduced risk of ventriculomegaly on MRI (OR = 0.46, 95% CI, 0.22–0.95; p = 0.03) and cUS (OR = 0.38, 95% CI, 0.0–0.93; p = 0.034). Infants carrying heterozygous (T/C) genotype at IL28B rs12979860 had an increased risk of cystic lesions on cUS (OR = 3.31, 95% CI, 1.37–8.01; p = 0.0064) and MRI (OR = 4.97, 95% CI, 1.84–13.43; p = 0.001), and an increased risk of ventriculomegaly on MRI (OR = 2.46, 95% CI, 1.03–5.90; p = 0.04). No other associations between genotyped SNPs and neuroimaging results were found. This is the first study demonstrating new associations between SNPs of IL1B and IL28B and abnormal neuroimaging in infants with cCMV.