Association of vitamin D level and vitamin D receptor A-1012G polymorphism with psoriasis – case control study

Objective of the study was to find the association of vitamin D receptor (VDR) polymorphisms (Fokl, Taql and Apal) with vitamin D levels in diabetic foot ulcer (DFU) patients in South India. In this case-control study, plasma vitamin D levels and VDR genotype frequencies of 70 cases (DFU patients) were compared with 70 diabetic (diabetes mellitus [DM] [non-DFU]) patients and 70 apparently healthy controls (HC) from South India. Plasma vitamin D levels were measured using the ELISA technique, and genotyping of VDR polymorphisms was carried out using real-time polymerase chain reaction. Logistic regression was used to find the association between DFU versus HC and DFU versus DM traits. Association analysis was performed based on additive, dominant and recessive models with age and gender as covariates. A 45.7% of DFU patients have sufficient vitamin D levels than 48.6% and 40% of DM patients and HC, respectively. Linkage disequilibrium analysis for DFU versus HC and DFU versus DM traits shows that single nucleotide polymorphisms (SNPs) Taq1 (rs731236) and Apal (rs7975232) are in strong linkage disequilibrium in DFU patients. The alleles and genotype frequencies were similar in all three groups. Although the additive model does not show statistical significance, age and sex correlate with the three SNPs (Fokl, Taql and Apal). No association was found between VDR gene polymorphisms and vitamin D levels in DFU patients in Southern India. On the other hand, age and sex correlate with the three SNPs.

Vitamin K epoxide reductase complex subunit 1 (VKORC1 ) polymorphism influences the anticoagulation response subsequent to vitamin K intake: a pilot study.

Background Preeclampsia has a multifactorial-yet-elusive etiology. Recent reports suggest a link between preeclampsia and vitamin D (VD) metabolic axis. Genetic variations like single-nucleotide polymorphisms (SNPs) of vitamin D receptor (VDR) gene can alter the metabolic role of VD, which have been shown by several genetic association studies. However, there is discordance among these studies. Objective The current study aimed to investigate the association of VDR gene polymorphism (ApaI) and VD deficiency with risk of developing preeclampsia. Patients and Method In this case–control study, 40 preeclamptic and 40 normotensive pregnant women were compared for VD status and VDR gene polymorphism. Serum 25-hydroxyvitamin-D [25(OH) D] level was determined by enzyme-linked immunosorbent assay (ELISA) and VDR gene polymorphism Apa1 was analyzed by Allele specific polymerase chain reaction (AS-PCR) using sequence specific primers. Results Serum levels of 25(OH) D were very low but comparable in both preeclamptic and normotensive pregnant women. The difference between the two groups were not statistically significant (p = .423). VDR gene polymorphism ApaI (rs7975232) was found not to have significant association with the risk of developing preeclampsia. The frequencies of wild genotype (GG) in preeclamptic and normotensive women were 27.5% and 22.5% respectively. A total of 25% of preeclamptic women had mutant homozygous genotype (TT) and 17.5% of normotensive women had mutant homozygous genotype. The frequency of mutant heterozygous genotype (GT) in preeclamptic patients was 47.5% and in normotensive women was 60%. The variation of wild and mutant genotypes between the two groups was not statistically significant (p > .05). Conclusion This study showed that VDR gene polymorphism (ApaI) and VD deficiency are not associated with the risk of preeclampsia.

The study was conducted to investigate the relationship between vitamin D receptor (VDR) gene rs2228570 and rs1544410 polymorphisms and pancreatic cancer (PC). Two hundred fifty-eight PC patients and 385 healthy controls were enrolled in this study. The genotypes of rs2228570 and rs1544410 were assayed using the polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. Univariate and multivariate logistic regression analyses were applied to determine the association between PC-onset risk and VDR gene polymorphisms. Contingency table analysis was performed to evaluate the relationship between the gene polymorphisms and clinicopathological tumor features such as location, pathological differentiation, and the TNM classification of PC. In rs2228570, the T loci and genotypes with T allele could increase the risk of PC; in rs1544410, the G loci and genotypes AG + GG could decrease the onset risk of PC significantly. The contingency table analysis indicated that the rs2228570 polymorphisms were correlated with the pathological differentiation of PC significantly, and the rs1544410 polymorphisms were correlated with the TNM classification of PC significantly. In conclusion, the VDR gene polymorphisms were correlated with incidence, pathological differentiation, and the TNM classification of PC significantly in our study population. So, the VDR polymorphisms have important implications in the incident rate and survival rate of PC.

Background: Non-specific low back pain (NSLBP) is a prevalent condition that significantly impacts the quality of life, particularly among young adult females. It leads to decreased physical fitness, compromised balance and endurance, and increased disability, affecting daily activities and overall well-being. Objective: The objective of this study was to assess the effects of NSLBP on cardiopulmonary endurance and balance in young adult females and to explore the implications for healthcare management and intervention strategies. Methods: This observational cross-sectional survey involved 60 female participants aged 18-40 years, experiencing NSLBP without underlying pathological conditions. The study employed convenience sampling at the University of Lahore Gujrat Campus over a six-month period. Measures included the Visual Analogue Scale (VAS) for pain, the Oswestry Disability Index (ODI) for disability assessment, the Time Up and Go (TUG) test for balance, and the Rockport Fitness Test for evaluating cardiopulmonary endurance. Statistical analysis was conducted using SPSS version 25, with T-tests for quantitative data and Chi-square tests for qualitative data. A p-value of ≤ 0.05 was considered statistically significant. Results: The majority of participants (66.7%) were in the 18-23 age group. According to the VAS, 43.3% reported severe pain, and 33.3% reported moderate pain. The ODI revealed that 60% of participants had minimal disability. Cardiopulmonary endurance analysis showed that 43.33% of participants had poor endurance, and 31.67% had very poor endurance. The TUG test indicated compromised balance, with a significant relationship between NSLBP and balance (p < 0.05). Statistical analysis further highlighted significant associations between NSLBP with age and cardiopulmonary endurance but not with BMI. Conclusion: NSLBP significantly affects cardiopulmonary endurance and balance among young adult females, indicating the need for a multidisciplinary approach in management and intervention. This study emphasizes the importance of incorporating physical therapy and lifestyle modifications to improve balance, endurance, and overall quality of life in individuals with NSLBP.

A Functional Polymorphism of Toll-Like Receptor 4 Gene Increases Risk of Gastric Carcinoma and Its Precursors

Understanding Study Design

The vitamin D receptor (VDR) is an important factor in activating immune response in different infectious diseases. The aim of the present study was to investigate the association between the VDR gene polymorphisms and pulmonary tuberculosis (PTB). The case control study was performed on 120 PTB patients and 131 healthy controls. Genetic analysis was performed by polymerase chain reaction and the restriction fragment length polymorphism method. The VDR Fok1 Ff genotype was associated with TB and the risk of PTB was two times higher in individuals with the Ff genotype. A higher frequency of f allele was observed in PTB patients and therefore, the f allele may be a risk factor for PTB susceptibility. There were no associations between the Taq1 and Bsm1 polymorphisms and PTB. In addition, haplotype analysis showed that the f-T-B and f-t-b haplotypes (Fok1, Taq1 and Bsm1) may have the potential to increase PTB susceptibility. In conclusion, the Ff genotype and f allele of the VDR Fok1 polymorphism were associated with PTB susceptibility. In addition, the f-T-B and f-t-b haplotypes may be the susceptible haplotypes for PTB.

Younger female adults are more vulnerable to depression than older females, potentially due to a greater affective response to inflammation. This randomized, double-blind, placebo-controlled study evaluated depressed mood and reward responsivity in response to an acute inflammatory challenge in younger as compared to older females. Low-dose endotoxin (0.8 ng/kg of body weight) or placebo was administered to younger (n = 40; age 25–44) and older (n = 53; age 60–80) healthy female adults. Participants provided blood samples and self-reported depressed mood pre-infusion and hourly over 9 h. The Effort Expenditure for Rewards Task (EEfRT) and Probabilistic Reward Task (PRT) assessed reward motivation, sensitivity, and learning at baseline and 2.5 h after infusion. Results showed that age moderated the effect of endotoxin on depressed mood (p = 0.0005), with endotoxin increasing depressed mood in younger (p <0.0001) but not older (p = 0.99) females. Age also moderated the effect of endotoxin on EEfRT reward sensitivity (p = 0.01), with a decrease in reward sensitivity in younger (p = 0.004) but not older (p = 0.43) females, with a similar trend observed for EEfRT reward motivation (p = 0.09). Age did not moderate the effect of endotoxin on PRT reward learning (p = 0.51); endotoxin decreased PRT reward learning in both groups (p = 0.04). Results indicate that younger females have heightened sensitivity to the effects of inflammation, resulting in greater increases in depressed mood and larger deficits in reward responsivity compared to older females. Interventions that target inflammation could be relatively more beneficial in the treatment of depression in younger females, as compared to those who are older. Trial Registration: ClinicalTrials.gov: NCT03256760; NCT03848715.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) and metabolic syndrome components among young adult females

The role of vitamin D in polycystic ovary syndrome

Vitiligo is a multifactorial skin disease with established role of genetics and autoimmunity in its pathogenesis. Vitamin D receptor (VDR) polymorphisms have been suggested to correlate with risk of vitiligo in some ethnic populations. On the other hand, cathelicidin, one of the innate immune system components, has a role in development of some chronic skin diseases and VDR regulates the expression of cathelicidin. We aimed to determine the plasma level of cathelicidin and its association with the VDR gene polymorphisms as well as plasma vitamin D level in patients with vitiligo. Ninety vitiligo patients and 90 non-vitiligo controls participated in this study. Blood levels of 25(OH) vitamin D and cathelicidin were determined with ELISA. Genotyping for VDR polymorphisms (ApaI, TaqI, FokI and BsmI) was done with RFLP-PCR method. Mean blood level of cathelicidin was significantly higher in vitiligo patients as compared to controls (P<.0001). Mean blood level of vitamin D was significantly lower in patients than controls (P=.01). Statistically significant differences were not observed for both genotype and allele frequencies of BsmI, ApaI and TaqI polymorphisms. There was a borderline increased risk of vitiligo in over-dominant model of FokI polymorphism with OR=1.8 and P=.051. Our findings was suggestive of the potential role of cathelicidin in the pathogenesis of vitiligo; however, future evaluations are needed to determine its precise mechanism. Genetic study of VDR gene polymorphism was suggestive of increased risk of vitiligo in association with a FokI polymorphism in Iranian population.

Having in mind the relationships among oxidative stress, psoriasis and common disorders, the association between polymorphisms in the gene encoding the receptor for advanced glycation end products (RAGE) and plaque psoriasis, including patients with a personal history of diabetes mellitus, cardiovascular disorders, cancer and allergy, was investigated. The allele frequencies and genotype distribution combinations of the four polymorphisms in the RAGE gene (6p21.3, G82S, 1704G/T, 2184A/G and 2245A/G) were compared in a case-control study of 272 subjects (130 patients with plaque psoriasis and 142 healthy control subjects of comparable age and sex distribution). The polymerase chain reaction with subsequent restriction analysis was used for detection of genotype variants. There was a significantly higher frequency of the 2184G allele of the 2184A/G RAGE polymorphism in psoriatic patients than in the control subjects (odds ratio 2.18, 95% CI 1.32-3.59, P=0.001). The 2184G allele occurred more often in psoriatic patients with a negative history of cardiovascular diseases (odds ratio 2.38, 95% CI 1.35-4.18, P=0.001, Pcorr=0.004), in those with a negative history of diabetes mellitus (odds ratio 2.05, 95% CI 0.1.22-3.45, P=0.004, Pcorr=0.012) and in those with a negative history of cancer (odds ratio 1.97, 95% CI 1.17-3.31, P=0.007, Pcorr=0.014) compared with the corresponding control subjects. We conclude that the 2184G allele of the RAGE gene is a significant risk factor for plaque psoriasis. The risk is associated with the non-presence of some common, especially cardiovascular, diseases in psoriatic patients.

Gallbladder Carcinoma (GBC) is relatively rare worldwide, accounting for 0.6-1.2% of all cancers. GBC is the most common hepatobiliary malignancy with aggressive biological behaviour. Adenocarcinoma is the predominant histological variant, while Squamous Cell Carcinoma (SCC) of the gallbladder comprises &lt;1% of GBC. It is most commonly found in elderly females and rarely found in young adult females. It is common in smokers and alcoholics. It is usually present in an advanced T staging or diagnosed only after a cholecystectomy done for a presumed benign condition. Therefore, SCC of the gallbladder has a poor prognosis. This case report discusses a rare case of SCC of the gallbladder in a 32-year-old young adult female presenting with abdominal pain and fever mimicking features of acute cholecystitis. Initial blood investigations show leucocytosis, and elevated serum Chorio Embryonic Antigen (CEA) and increased Cancer Antigen (CA) 19.9. Radiological evaluation suggested growth in the gallbladder, and she underwent open cholecystectomy, with fragments of the left and right lobes of the liver being removed to look for metastasis. Postoperative histopathology shows moderately differentiated SCC with infiltration into the serosa, fragments from both lobes of liver are free from infiltration and Immunohistochemistry (IHC) P63 shows moderate to strong nuclear positivity,confirming SCC. The final Impression was given as moderately differentiated SCC of the gallbladder- pT3NxMx. This case presents an unusual instance of SCC of the gallbladder in a young adult female.

Background Psoriatic arthritis (PsA) is a seronegative (rheumatoid factor-negative) usually Cyclic Citrullinated Peptide (CCP) antibody negative, immunologically triggered, chronic inflammatory joint disease within the framework of psoriasis.Psoriasis affects 2-4% of the general population.It is a common, chronic, relapsing/remitting, immune-mediated systemic disease characterized by skin lesions including red, scaly patches, papules and plaques, which usually itch.Vitamin D is actually a fat-soluble steroid prohormone that has endocrine, paracrine and autocrine functions. Aim of the Work:To investigate the level of serum vitamin D in patients with psoriatic arthritis and compare it with patients with psoriasis to show if there is a role of vitamin D in development of arthritis in psoriatic patients or not.Patients and Methods: This study is a cross sectional study in which fifty patients with psoriatic arthritis and psoriasis age range 16-50 years selected from those attending the outpatient clinic and inpatients of rheumatology, physical medicine &rehabilitation department, Al-Azhar university hospitals from 2017 to 2018 and divided into two groups: Group (A): (25) patients with psoriatic arthritis were diagnosed according to the criteria for psoriatic arthritis classification "CASPAR criteria".Group (B): (25) patients with skin psoriasis.In this study we measured of 25 hydroxy vitamin D3 using commercial ELISA kits, ESR, CRP, CBC, Blood urea, serum creatinine, Liver enzymes (SGOT & SGPT), Serum uric acid, Fasting blood glucose, RF, urine analysis, ANA, HCV Ab and HIV Ab.Plain x-ray on both hands postero-anterior view, Plain x-ray on lumbosacral spine antero-posterior and lateral views and Plain x-ray on both sacroiliac joints "cone" view.Results: There was female sex predicliction in psoriatic arthritis group.Otherwise, both groups were comparable regarding age, BMI, residence, co-morbid diseases, disease characteristics, and laboratory investigations, except significant increase of WBCs and inflammatory markers (ESR and CRP) in psoriatic arthritis group.Diseases severity was mild in 72%, moderate in 22% and severe in 6.0%; and there was statistically significant increase of moderate and severe disease in PA when compared to psoriasis group.vitamin D was sufficient in 32.0%, insufficient in 34.0% and deficient in 34.0%; and there was no significant difference between psoriasis and PA groups.In addition, vitamin D levels were increased in psoriasis when compared to PA groups.However, the difference was statistically non-significant.No significant relation was found between vitamin D from one side and each of patient characteristics, laboratory investigations (except significant positive correlation with hemoglobin and RBCs), disease characteristics (except significant inverse (negative) correlation with disease duration and disease severity), X-ray findings, and psoriatic arthritis disease activity indices.Conclusion: Vitamin D deficiency/insufficiency was common among psoriasis and psoriatic arthritis patients and the deficiency was significantly and inversely correlated with disease severity (PASI) and disease duration.Thus, is thought to play a role in development (or a consequence) of psoriasis.On the other hand, there was no correlation with PA disease activity and severity indices.Thus, the association seems to be linked to psoriasis proper.Vitamin D supplementation thought to have a potential therapeutic role in treatment of psoriasis.