[Research progress in the diagnosis of primary vitreoretinal lymphoma].

Primary vitreoretinal lymphoma (PVRL), the most prevalent intraocular lymphoma, is a subtype of primary central nervous system lymphoma (PCNSL) that often clinically mimics uveitis. It is a rare intraocular malignancy characterized by a dismal prognosis. The gold standard for PVRL diagnosis remains cytopathological examination. Additionally, auxiliary tests, such as clonal detection of tumor cells and cytokine analysis, have been employed. Moreover, recent years have witnessed the gradual development of novel molecular biomarkers and detection techniques. To optimize diagnostic strategies for PVRL patients, a comprehensive approach that integrates clinical manifestations, cytological examination, immunological assessment, and molecular biology analysis is indispensable. This article provides a comprehensive review of recent advancements in the diagnosis of primary vitreoretinal lymphoma.

Levels of peripheral IL-6 and CD4+ and CD8+ T cells and their prognostic significance in COVID-19.

OBJECTIVE: The aim of this study was to discuss the prognostic significance of peripheral interleukin-6 (IL-6) and CD4+ and CD8+ T cells in COVID-19. PATIENTS AND METHODS: Eighty-four COVID-19 patients were retrospectively analyzed and classified into three groups, including the moderate group (15 cases), the serious group (45 cases), and the critical group (24 cases). The levels of peripheral IL-6, CD4+, and CD8+ T cells and CD4+/CD8+ were determined for each group. It was assessed whether these indicators were correlated to the prognosis and death risks of COVID-19 patients. RESULTS: The three groups of COVID-19 patients differed significantly in the levels of peripheral IL-6 and CD4+ and CD8+ cells. The IL-6 levels in the critical, moderate, and serious groups were increased successively, but the changed levels of CD4+ and CD8+ T cells were just opposite to that of IL-6 (p<0.05). The peripheral IL-6 level increased dramatically in the death group, while the levels of CD4+ and CD8+ T cells decreased significantly (p<0.05). The peripheral IL-6 level was significantly correlated with the level of CD8+ T cells and CD4+/CD8+ ratio in the critical group (p<0.05). The logistic regression analysis indicated a dramatic increase in the peripheral IL-6 level in the death group (p=0.025). CONCLUSIONS: The aggressiveness and survival of COVID-19 were highly correlated with the increases in IL-6 and CD4+/CD8+ T cells. The fatalities of COVID-19 individuals remained at increased incidence due to elevated peripheral IL-6 levels.

[Research progress of medication treatment of pediatric noninfectious uveitis].

Pediatric uveitis accounts for 5% to 10% of all uveitis, most of which are noninfectious. Most cases have an insidious onset and are accompanied by many complications, which may lead to poor prognosis and intractable treatment. At present, traditional drugs that are commonly employed to treat pediatric noninfectious uveitis include local and systemic corticosteroids, methotrexate and other immunosuppressants. In recent years, the application of various biological agents has provided new means for the treatment of this kind of disease. This article reviews the progress of medication treatment of pediatric noninfectious uveitis.

[Current research on cytokine gene single nucleotide polymorphisms of Behcet's syndrome].

Behcet's syndrome (BS) is characterized by systemic vasculitis with unknown etiology. There is evidence that more than one mechanism underlies the pathogenesis of BS, involving genetic factors and environmental stimuli. Although human leucocyte antigen-B51 is by far the most strongly associated genetic factor to BS, it accounts for less than 20% of the genetic risk, which indicates that other genetic factors remain to be discovered. Cytokines are signal molecules of the immune system which modulate the inflammatory process of nearly all immune response. The single nucleotide polymorphism (SNP) of cytokine gene have been associated with BS in many studies, involving T helper cell 1-type cytokines, interleukin 1 cytokine, interleukin 17 and chemotactic cytokine. The impact of different SNPs on BS varies, most of which affect the risk of disease, while the remaining affect the phenotype, the cumulative effect of these minor genes (SNPs) might be the genetic mechanisms of BS pathogenesis. (Chin J Ophthalmol, 2020, 56: 876-880).

[Effect of low dose ionizing radiation on peripheral blood cells of radiation workers in nuclear power industry].

Objective: To investigate the effects of long-term ionizing radiation on peripheral blood cells of nuclear power workers. Methods: In March 2019, a total of 530 radiation exposed workers in the nuclear power industry who underwent in-service radiation occupational health examination in Guangzhou occupational disease prevention and control hospital in 2018 and with service age ≥1 year were selected as the radiation group. At the same time, 545 workers in nuclear power industry were selected as control group. According to the methods and requirements of GBZ 235-2011 ＂technical specification for occupational health monitoring of radiation workers＂ and GBZ 98-2017 ＂health requirements for radiation workers＂, the occupational health monitoring data were collected, and the change rules of peripheral blood cells in the two groups were analyzed. Results: Compared with the control group, the total number of WBC, NEUT, LYMP, Hb, MCV and MCHC in radiation group were lower than those in control group (P<0.05) , and the difference was statistically significant (P<0.05) . The MPV increased significantly (P<0.05) . Compared with the control group, the abnormal rate of WBC and Hb in the radiation group was higher than that in the control group (P<0.01) , but there was no significant difference in the abnormal rate of RBC and PLT (P>0.05) . Conclusion: Low dose ionizing radiation has a certain cumulative damage effect on peripheral blood cells of radiation workers in nuclear power industry. The change rules of different cell subtypes are different, and the changes of WBC and PLT appear earlier.

[Measurement of proximal enamel thickness of 182 permanent teeth].

Objective: To measure the proximal enamel thickness (PET) at the mesial and distal contact areas of the permanent teeth and to provide a reference for interproximal enamel reduction (IPR). Methods: From May 2016 to February 2018, 182 isolated permanent teeth were collected and screened from patients who underwent extraction at Department of Oral and Maxillofacial Surgery, Capital Medical University School of Stomatology. These teeth were extracted for orthodontic purpose or due to severe periodontitis. The patients having teeth extracted were all Beijing residents, Han nationality, and aged (39.5±10.6) years. Ninety percent of the teeth came from patients under 50 years old. These teeth were classified according to different tooth type. The mesial and distal contact areas of these teeth were marked with fluid resin. The isolated teeth were scanned using micro-CT and the enamel thickness was measured and analyzed. The parameters measured included mesial PET (PETm), distal PET (PETd), the distance from mesial contact area to occlusal plane (CAm-OP), the distance from distal contact area to occlusal plane (CAd-OP), the distance from mesial contact area to the cementoenamel junction (CAm-CEJ), the distance from distal contact area to cementoenamel junction (CAd-CEJ) and tooth width (TWmd). Results: The PET gradually increased from the anterior tooth area [(0.63±0.16) mm] to the molar area [(1.46±0.25) mm]. The sum of the PET from the second molar to the contralateral second molar in the maxillary dentition was 31.60 mm, and that of the PET from the second molar to the contralateral second molar in the mandibular dentition was 29.68 mm. The contact areas were located on the occlusal third of the proximal walls of anterior teeth and the middle third of the proximal walls of posterior teeth. The PET were positively correlated with the tooth width between the mesial and distal contact areas (P<0.05). Conclusions: The PET was thinner in the incisor area and thicker in the molar area. IPR should be carried out close to the occlusal side of the proximal walls in anterior teeth and the cementoenamel junction side of the proximal walls in posterior teeth.

[Clinical features of patients with Behcet's uveitis].

Objective: To characterize the clinical features of patients with Behcet's uveitis. Methods: Retrospective case series study. Medical records of patients who were diagnosed as Behcet's uveitis in Peking Union Medical College Hospital between January 1998 and November 2015 were retrospectively reviewed. Information about the clinical manifestation, complication, best corrected visual acuity (logarithm of the minimum angle of resolution) and medication was collected. The correlation of visual acuity and the disease course, as well as inflammation relapse times before and after biological agents applied was analyzed. Chi square test and Wilcoxon signed-rank test were applied for statistical analysis. Results: A total of 132 patients (233 eyes) with Behcet's uveitis were included, among which 104 (78.8%) were male and 28 (21.2%) were female, with statistically significant difference (χ(2)=43.76, P<0.01). The average age at the onset of uveitis was (28.9±8.7) years, with most patients at 21-40 years (102 cases, 77.3%). Oral aphthae (132 cases, 100.0%) were the most frequent extraocular manifestations, followed by dermatologic lesions (103 cases, 78.0%), genital ulcers (90 cases, 68.2%), arthritis (44 cases, 33.3%) and positive pathergy test (39 cases, 29.5%). Ocular involvement was bilateral in 76.5% (101 cases) of the patients, and panuveitis was the most common type (110 cases, 83.3%). Complications were seen in 80.7% (188/233) of the eyes, with cataract (58.8%, 137/233) and macular edema (59.1%, 114/193) being the most common anterior and posterior segment complications, respectively. At the eighth year of uveitis, best corrected visual acuity decreased to less than 0.3 in 20.9% (9/43) of the eyes, and more than 1.0 in 39.5% (17/43) of the eyes. A combination of glucocorticoids and immune modulators remained the first line therapy (97.0%, 128/132) for Behcet's uveitis. For 16 refractory cases, an addition of biological agents significantly reduced the inflammation relapse [0.5 (0.0, 1.5) times per year vs. 4.0 (1.0, 5.5) times per year, Z=-2.81, P=0.005]. Conclusions: Behcet's uveitis mainly affects working-age males and manifests as bilateral panuveitis. Complications are commonly seen in uveitic eyes. Patients' visual acuity is significantly impaired. A combination of glucocorticoids and immune modulators is effective for most patients, but for refractory cases, an addition of biological agents provides better effects. (Chin J Ophthalmol, 2020, 56: 217-223).

[Analysis of unplanned reoperation following vitreoretinal surgery].

Objective: To determine the incidence of unplanned reoperation following vitreoretinal surgery and identify the reasons for unplanned reoperations. Methods: Case records of all patients undergoing vitreoretinal surgery at Peking Union Medical College Hospital between June 2014 and June 2017 were reviewed to determine the incidence of unplanned reoperations during the primary admission and within 90 days following vitreoretinal surgery. Results: A total of 3 356 case records were reviewed. During the primary admission, 97 times of unplanned reoperation occurred in 81 cases [45 males and 36 females, aged (47.3±16.8) years].The incidence of unplanned reoperation was 2.4% (81/3 356). The most common primary diseases were retinal detachment (25 cases, 30.9%), proliferative diabetic retinopathy (23 cases, 28.4%) and silicone oil filled eye (17 cases, 21.0%). The most common reasons for unplanned reoperation were new onset or recurrent retinal detachment (33 times, 34.0%), increased intraocular pressure (23 times, 23.7%), as well as hyphema and inflammation (16 times, 16.5%). The percentages of the primary diseases and reasons for unplanned reoperation within 90 days following vitreoretinal surgery were not significantly different when compared with those during the primary admission. Desired results could be achieved in all cases after unplanned reoperation. Conclusions: The primary diseases of unplanned reoperation for vitreoretinal surgery are complicated retinal detachment, diabetic retinopathy and silicone oil filled eyes. New onset or recurrent retinal detachment, increased intraocular pressure, hyphema and inflammation are common causes of reoperation.

[The presentations of uveitis on OCTA images and interpretations].

Optical coherence tomography angiography (OCTA) can reflect the vascular morphological changes of various types of uveitis, including flow void, hypoperfusion, capillary abnormalities, capillary network disorders and choroidal neovascularization. Moreover, OCTA is featured of particular quantification functions, such as measurement of the areas of foveal avascular zone, choroidal neovascularization, vascular density and flow index. Despite certain limitations, its characteristics of non-invasiveness and capabilities of depicting vascular details are helpful to the observation and follow-up of uveitis. As current interpretation of the OCTA images for uveitis is not thorough enough, hence further analysis of the images is needed to improve its application on uveitis. (Chin J Ophthalmol, 2019, 55: 392-396).

Parenchymal hyperdensity on C-arm CT images after endovascular therapy for acute ischaemic stroke predicts a poor prognosis.

AIM: To investigate whether hyperdense areas (HDAs) observed after endovascular treatment on multisection computed tomography (CT) are related to outcome. MATERIALS AND METHODS: Data on 82 patients with acute anterior circulation ischaemic stroke resulting from intracranial large artery occlusion were analysed retrospectively All patients underwent mechanical thrombectomy and/or emergency angioplasty, and partial or complete recanalisation was successfully achieved. C-arm CT was performed immediately after endovascular treatment for all patients. Clinical and radiological data were compared between patients with and those without HDA and between patients with good and those with poor outcomes. RESULTS: Compared with non-HDA patients, HDA patients were more likely to present with severe neurological deficits (admission National Institutes of Health Stroke Scale [NIHSS] score: 18 versus 16, p=0.037) and had a higher number of stent retriever passes performed (2.9±1.3 versus 1.4±1, p<0.001), longer onset-to-presentation times (229±78 versus 171±90 minutes; p=0.002), longer onset-to-recanalisation times (418±94 versus 331±105 minutes; p<0.001), and longer puncture-to-recanalisation times (103±47 versus 69±42 minutes; p=0.001). Fewer HDA patients had a good prognosis (35.7% versus 70%, p<0.001). Multivariate analysis showed the presence of HDAs was an independent negative prognostic factor (OR=0.208; p=0.002). CONCLUSION: HDAs on C-arm CT appear to be common in patients with acute ischaemic stroke who underwent successful endovascular treatment. HDA presence suggests a poor prognosis despite successful reperfusion.

[Clinical features of glucocorticoid eye drops induced ocular hypertension in pediatric and adult uveitic eyes].

Objective: To investigate the clinical features of glucocorticoid eye drops induced ocular hypertension in pediatric and adult uveitic eyes. Methods: Retrospective survey of consecutive uveitic patients attending referral service at Peking Union Medical College Hospital from March 2013 to August 2017. Incidences of glucocorticoid eye drops induced ocular hypertension were compared between the pediatric and adult uveitic groups. The clinical patterns of 1% prednisolone acetate eye drops induced ocular hypertension in pediatric and adult uveitic eyes were also investigated. Data were analyzed using the Mann-Whitney test and the χ(2) test. Results: The clinical data of 1 138 uveitic eyes [677 patients; 331 males and 346 females; mean age (31±16) years]receiving corticosteroid eye drops were reviewed, among which 246 eyes (143 patients) had pediatric uveitis and 892 eyes (534 patients) had adult uveitis. The incidence of glucocorticoid eye drops induced ocular hypertension was higher in pediatric eyes (39.8%, 98/246) as compared to adults (29.1%, 260/892) (χ(2)=9.880, P=0.002). One hundred and thirty eyes (75 patients) with 1% prednisolone acetate induced ocular hypertension were included in the clinical pattern analysis, including 49 [28 patients; 15 males and 13 females; mean age (11±3) years] pediatric and 81 [47 patients; 22 males and 25 females;mean age (34±12) years] adult uveitic eyes. No differences were found in daily doses of 1% prednisolone acetate between the pediatric group [4.60 (3.46, 5.36) drops/day] and the adult group [4.00 (3.30, 4.88) drops/day; Z=-1.675, P=0.094]. But the duration of medication in pediatric eyes [4.71 (2.79, 6.36) weeks] was significantly shorter as compared to the adults [6.00 (4.86, 9.00) weeks; Z=-3.446, P<0.001]. The intraocular pressure (IOP) was 26.00 (24.00, 31.00) mmHg (1 mmHg=0.133 kPa) in pediatric uveitic eyes and 26.00 (23.30, 31.15) mmHg in the adults, which showed no statistical significance (Z=-0.231,P=0.818). To achieve effective IOP control, 79.6% (39/49) of pediatric and 54.3% (44/81) of adult eyes received IOP-lowering drug therapy (χ(2)=8.447,P=0.004). And during the follow-up, the withdrawal rate of IOP-lowering drugs was much lower in pediatric eyes (48.7%, 19/39) as compared to the adult group (72.7%, 32/44) (χ(2)=5.031, P=0.025). Conclusion: Compared with adult patients with uveitis, children with uveitis are more prone to IOP elevation, which is more difficult to control after the use of glucocorticoid eye drops. (Chin J Ophthalmol, 2018, 54: 839-842).

[The diagnostic investigations should be efficient for patients with uveitis].

Uveitis is a common and etiologically complex disease. The diagnosis of uveitis is mainly based on clinical findings, and no ancillary test is needed for diagnosis of the most common uveitis entities in China. Ancillary tests, however, are needed to identify the underlying cause when the clinical presentation points to some specific disease entity, and when infectious uveitis or masquerade syndrome is suspected. A variety of ophthalmic imaging techniques and laboratory tests analyzing blood or intraocular fluid are currently available for etiological identification in uveitis as well as for disease follow-up. When these tests are considered, the less invasive, expensive and time-consuming ones should be chosen. (Chin J Ophthalmol, 2017, 53: 721-723).

[Optical coherence tomography angiography of acute Vogt-Koyanagi-Harada disease].

Objective: To measure vascular density in retinal and choroidal capillary layers by optical coherence tomography angiography (OCTA) and to explore their potential clinical values in Vogt-Koyanagi-Harada disease (VKH). Methods: This is a cross-sectional case-control study. Twenty-one acute VKH cases presented to Peking Union Medical College Hospital between April 2015 and July 2015 and 49 healthy controls were enrolled in this study. OCTA was performed with a split-spectrum amplitude-decorrelation angiography-optical coherence tomography (SSADA-OCT) system borrowed from Optovue Inc. Vascular densities of the capillary layers were analyzed by the built-in software. Bilateral independent sample t-test was used to compare retinal and choroidal vascular density of eyes in acute phase VKH with healthy controls. Spearman correlation test was used to analyze the correlation between the vascular density of retina and choroid in acute phase VKH and LogMAR best corrected visual acuity (BCVA). Results: Mean vascular density of superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) in eyes of the acute VKH group were statistically lower than those of healthy control group (51.56%±2.88%, 56.51%±2.31%, 58.14%±2.10% vs. 53.55%±2.51%, 58.14%±2.10%, 58.14%±2.10%, t=-3.890, 3.910,-6.554, all 3 P values were<0.01). In VKH patients, eyes with retinal detachment (RD) had statistically lower mean vascular density in the CC layer than those without (NRD) (63.46%±2.19% vs. 65.85%±1.79%, t=3.890, P<0.01), while no statistically significant differences were found in vascular densities of SCP and DCP layers between RD and NRD eyes. Spearman's correlation test revealed a negative correlation between vascular density of the CC layer and logMAR BCVA(r=-0.437, P<0.01), while no statistically significant associations were found between logMAR BCVA and vascular densities of SCP and DCP. Conclusions: OCTA can be used for quantitative detection of vascular density of retina and choroidal capillary in acute VKH. There is circulatory disturbance in SCP, DCP and CC of acute VKH. Vascular density of CC is associated with visual acuity and retinal detachment. (Chin J Ophthalmol, 2017, 53: 735-739).

[The fundus manifestations and SD-OCT findings of patients with acute Vogt-Koyanagi-Harada disease].

Objective: To conclude the characteristics of fundus appearance and spectral domain optical coherence tomography(SD-OCT) findings of patients with acute Vogt-Koyanagi-Harada (VKH) disease. Methods: The clinical data of 17 patients (34 eyes) diagnosed of acute VKH in Peking Union Medical College Hospital from Jan. 2012 to Dec. 2014 were studied retrospectively.Examinations included visual acuity, slit lamp, fundus, color fundus pictures, FFA and SD-OCT. Results: Eight men and 9 women were enrolled with mean age of (40.5±11.6) years old ranging from 26.0 to 62.0 years old. Vision acuity of their first consultations were as follows: 14 eyes (41.2%) were below 0.01-0.09, 17 eyes(50%) were among 0.1-0.3, 3 eyes (8.8%) were among 0.4-0.7. All patients were divided into 3 groups according to their fundus appearance: 14 eyes (41.2%) were optic disc swelling-type, 10 eyes (29.4%) were retinal detachment type and 10 eyes(29.4%)were mixed type. Subretinal fluid and serous retinal detachment appears in SD-OCT of all 34 eyes, with highly reflective signals in detached area. Other common characters were also noticeable, suh as RPE folds(19 eyes, 55.9%), subretinal septa (16 eyes, 47.1%) and internal limiting membrane(ILM) fluctuation (8 eyes, 23.5%). In addition, SD-OCT features were in accordance with multilobular dye pooling at late period of FFA. Conclusion: SD-OCT of acute VKH presents some typical features: subretinal fluid and serous retinal detachment, RPE folds, ILM fluctuation, and subretinal septa.(Chin J Ophthalmol, 2017, 53: 436-439).

[Clinical features, risk factors and progresses on treatment of recurrent Vogt-Koyanagi-Harada disease].

Vogt-Koyanagi-Harada disease(VKH) is a bilateral, granulomatous panuveitis associated with central nervous system, auditory, and integumentary manifestations. Clinically, VKH usually responds well to early aggressive glucocorticosteroid treatment and may be cured without any clinically significant sequelae. Some patients, however, may enter the chronic recurrent phase, which may result in marked loss of vision due to complications such as complicated cataract, secondary glaucoma and maculopathy. Recurrent VKH is mainly characterized by anterior uveitis associated with thickening of the choroid. Initial poor visual acuity, severe anterior chamber reaction, choroidal folds,rapid tapering of systemic corticosteroids or inadequate duration of treatment, and development of extraocular manifestations may be risk factors of disease recurrence. Prolonged glucocorticosteroid treatment has been suggested as effective strategy for recurrence of VKH. The positive effects of other immunosuppressive agents and biologic agents on treatment of chronic recurrent and refractory VKH have been gradually recognized by the uveitis community. (Chin J Ophthalmol, 2017, 53: 317-320).

Lack of association between CARD10/CARMA3 tag SNPs and psoriasis vulgaris in the southern Chinese population.

Previously, we determined that the CARD11 rs4722404 single nucleotide polymorphism (SNP) increases risk of early-onset psoriasis vulgaris (PsV). Moreover, the CARD14 gene polymorphism c.C2458T (p.Arg820Trp) is associated with clinical features of this disease. CARMA1/CARD11, CARMA2/CARD14, and CARMA3/CARD10 are conserved across many species and constitute a family of proteins, all of the members of which contain various functional domains characteristic of this group. The NF-κB signaling pathway, regulated by the CARMA family of scaffold proteins and its eponymous component, is a crucial mediator in the pathogenesis of psoriasis. However, little is known about the association between CARMA3/CARD10 and PsV. The aim of this study was to evaluate the relationship between the gene encoding this protein and risk of PsV in the southern Han Chinese population. Genomic DNA from 568 individuals of southern Chinese origin, including 355 patients with PsV and 213 control subjects, was analyzed. We selected seven tag SNPs in the CARMA3/CARD10 gene and genotyped them by the SNaPshot assay. Our results identified no significant association between these SNPs and PsV in the Chinese population examined. Future studies should focus on the potential function of the CARMA3/CARD10 gene in the pathogenesis of PsV.

[Behcet's disease and infection].

Behcet's disease (BD) is a systemic vasculitis of unknown etiology. Uveitis, which is common and therapeutically challenging, is the major ocular manifestation of BD. Researches have shown that, in addition to the genetic components (e.g. HLA-B51), environmental factors such as infection also play important roles in the pathogenesis of BD. In recent years, with the advances in bio-detecting technologies, accumulating evidence has shown an association between microbial infections and previously believed non-infectious immune disorders. Specifically, there has been increasing research interest in roles of infection in pathogenesis of BD. A variety of microbes, including streptococcus sanguis, staphylococcus aureus, intestinal flora, herpes simplex virus and etc., have been suggested to be involved. The objective of this article is to review current research progress concerning BD and infection, as well as to provide some recommendations for future investigations into this subject. (Chin J Ophthalmol, 2016, 52: 636-640).

Reference gene selection for gene expression studies in lily using quantitative real-time PCR.

Quantitative real-time polymerase chain reaction (qRT-PCR) is an important technology used to analyze gene-expression levels. Reference genes, which are assumed to be expressed consistently across various developmental stages and in different tissues, were selected for expression level analysis. Using digital gene expression technology, we selected nine reference genes (18S, EF, CYCOL, SAND, GAPDH, ACTIN, BHLH, TIP, and Clathrin) as candidate reference genes for further study. Using three different analysis methods (GeNorm, NormFinder, and BestKeeper), a total of 144 lily (Lilium x formolongi "Raizan 3") samples were analyzed. The samples were collected from four different tissues under various developmental stages. In addition, leaves treated with different plant hormones were collected and analyzed. The data showed that the stability of the nine reference genes differed among samples, but TIP, EF, Clathrin, and BHLH could be identified as the most stable genes overall. In addition, the relative expression level of LfFT in different lily tissues with the competence to flower was also analyzed to verify the selected reference genes. This study constitutes an important source for selecting reference genes when analyzing the expression patterns of flowering time and floral development regulation genes in lily cultivars.

Interactions between adiposity and genetic polymorphisms on the risk of psoriasis.

BACKGROUND: Adiposity is a known risk factor for psoriasis. Genome-wide association studies (GWAS) have identified a number of genes associated with risk of psoriasis while the evidence on gene-environment interactions in psoriasis is very sparse. OBJECTIVES: To investigate the effect modification by adiposity measures on the association between single-nucleotide polymorphisms (SNPs) from published GWAS and risk of psoriasis. METHODS: Our psoriasis GWAS dataset comprised 9194 participants, including 337 individuals with psoriasis and 8857 controls from six GWAS, nested within the Nurses' Health Study (NHS), NHS II, and Health Professionals' Follow-up Study. Clinician-diagnosed psoriasis was ascertained with high validity. For stratified analyses, body mass index (BMI) was dichotomized at 25, and waist circumference was dichotomized at 30 (women) and 36 inches (men), while waist-hip ratio (WHR) was dichotomized at 0·8 (women) and 1·0 (men). RESULTS: Forty-one out of 44 previously reported psoriasis-related SNPs were included in our GWAS datasets. After excluding those with high linkage disequilibrium, 33 remained in the analysis. There were significant interactions between BMI and two SNPs in the IL12B (rs3212227) and IL23R (rs7530511) genes. Further analysis of these two SNPs indicated interactions between rs3212227 and waist circumference or WHR [P for interaction (P ) < 0·05], but not for rs7530511. These observations were confirmed among participants without type 2 diabetes or coronary heart disease. The interactions remained after simultaneously adjusting for BMI as a continuous variable. In addition, we did not observe a significant main effect for rs7530511. CONCLUSION: The association between a polymorphism in IL12B and psoriasis risk may be modified by measures of overall and central adiposity.