Effect of vitamin D binding protein gene polymorphism on susceptibility and prognosis of severe acute pancreatitis / 中华危重病急救医学

OBJECTIVE@#To investigate the effect of vitamin D binding protein (DBP) gene polymorphism on susceptibility and prognosis of severe acute pancreatitis (SAP).@*METHODS@#A prospective study was conducted. Eighty-three patients with SAP who were admitted to the department of general surgery of Tianjin Fifth Central Hospital from March 2018 to March 2021 were selected as the research objects, and 83 healthy people in the same period were selected as controls. Peripheral blood RNA was extracted and reverse transcribed into cDNA, and the genotype and allele frequency of DBP gene rs7041 locus were detected by fluorescence quantitative analyzer. Hardy-Weinberg equilibrium was used to test the genetic balance. On the day of admission, serum C-reactive protein (CRP) level was detected by scattering immunoturbidimetry, serum procalcitonin (PCT) level was detected by electrochemiluminescence, serum DBP level was detected by enzyme-linked immunosorbent assay (ELISA), and neutrophil to lymphocyte ratio (NLR) was calculated automatically by the instrument. The length of intensive care unit (ICU) stay, the length of hospital stay and prognosis during hospitalization of patients were statistically analyzed. Multivariate Logistic regression analysis was used to screen the influencing factors of SAP occurrence.@*RESULTS@#The results of Hardy-Weinberg equilibrium test showed that the distribution of gene polymorphisms in the two groups of subjects conformed to the law of genetic equilibrium. The frequencies of TT genotype and T allele of DBP gene rs7041 locus in the patients of SAP group were significantly higher than those in the healthy control group [TT genotype: 34.94% (29/83) vs. 9.64% (8/83), T allele: 55.42% (92/166) vs. 38.55% (64/166), both P < 0.01], and the frequency of GT genotype was significantly lower than that in the healthy control group [40.96% (34/83) vs. 57.83% (48/83), P < 0.05]. There was no significant difference in the frequency of GG genotype between the healthy control group and SAP group [32.53% (27/83) vs. 24.10% (20/83), P > 0.05]. Further multivariate Logistic regression analysis showed that TT genotype [odds ratio (OR) = 2.831, 95% confidence interval (95%CI) was 1.582-5.067, P < 0.001] and T allele (OR = 2.533, 95%CI was 1.435-4.472, P < 0.001) of DBP gene rs7041 locus were independent risk factors for SAP in healthy people, while GT genotype was a protective factor for SAP (OR = 0.353, 95%CI was 0.143-0.868, P = 0.041). The levels of CRP, PCT, NLR and DBP in patients with TT genotype of DBP gene rs7041 locus were significantly higher than those in patients with GG/GT genotype on the day of admission in SAP group [CRP (mg/L): 43.25±13.25 vs. 31.86±12.83, PCT (μg/L): 1.53±0.24 vs. 1.21±0.20, NLR: 3.15±0.53 vs. 2.71±0.48, DBP (μg/L): 87.78±19.64 vs. 70.58±18.67, all P < 0.01]. The length of ICU stay in patients with TT genotype of DBP gene rs7041 locus in SAP group was significantly longer than that in patients with GG/GT genotype (days: 11.35±1.58 vs. 9.71±1.35, P < 0.01). The length of hospital stay of patients with TT genotype was longer than that of patients with GG/GT genotype (days: 23.41±3.64 vs. 23.17±3.57), and the in-hospital mortality was higher than that of patients with GG/GT genotype [34.48% (10/29) vs. 29.63% (16/54)], but the difference was not statistically significant (both P > 0.05).@*CONCLUSIONS@#The risk of SAP was significantly increased in patients with TT genotype of rs7041 locus of DBP gene, and the mechanism may be related to the increase of DBP expression. And carrying the TT genotype will prolong the ICU hospitalization time of SAP patients, but the effect on prognosis is not obvious.

Genetic, sociodemographic and lifestyle factors associated with serum 25-hydroxyvitamin D concentrations in Brazilian adults: the Pró-Saúde Study / Fatores genéticos, sociodemográficos e de estilo de vida nas concentrações séricas de 25-hidroxivitamina D em adultos brasileiros: o Estudo Pró-Saúde / Factores genéticos, sociodemográficos y estilo de vida asociados con la concentración sérica 25-hidroxivitamina D en adultos brasileños: Estudio Pro-Salud

This study aims to investigate factors associated with serum 25-hydroxyvitamin D [25(OH)D] concentration in Brazilian adults considering sociodemographic and lifestyle factors, as well as vitamin D-related single nucleotide polymorphisms (SNPs). This is a cross-sectional study (n = 491; 34-79y; 251 women), nested within a prospective cohort (Pró-Saúde Study). Associations between serum 25(OH)D and sociodemographic characteristics, diet, use of supplement, physical activity, season of blood collection, body fat, skin type, sun exposure index, and SNPs CYP2R1-rs10741657 and GC-rs2282679 were explored by multiple linear regression. The prevalence of serum 25(OH)D < 50nmol/L was 55%. Serum 25(OH)D was lower among women (β = -4.38; 95%CI: -8.02; -0.74), those with higher visceral fat (β = -4.02; 95%CI: -5.92; -2.12), and those with AC and CC genotypes for GC-rs2282679 (β = -6.84; 95%CI: -10.09; -3.59; β = -10.63; 95%CI: -17.52; -3.74, respectively). Factors directly associated with serum 25(OH)D included summer (β = 20.14; 95%CI: 14.38; 25.90), intermediate skin type (β = 6.16; 95%CI: 2.52; 9.80), higher sun exposure (β = 0.49; 95%CI: 0.22; 0.75), vitamin D intake (β = 0.48; 95%CI: 0.03; 0.93), and physical activity (β = 4.65; 95%CI: 1.54; 7.76). Besides physical activity, diet, and sun exposure, non-modifiable factors, such as GC genotypes must be considered when evaluating vitamin D insufficiency in mixed-race populations. Moreover, high visceral fat in association with poorer vitamin D status deserve attention given that both conditions are unfavorably related with chronic and acute health outcomes.

Este estudo teve como objetivo investigar fatores associados com as concentrações séricas de 25-hidroxivitamina [25(OH)D] em adultos brasileiros de acordo com fatores sociodemográficos e de estilo de vida, assim como de polimorfismos de nucleotídeo único (SNPs) relacionados à vitamina D. Este é um estudo transversal (n = 491; 34-79 anos; 251 mulheres) aninhado em uma coorte prospectiva (Estudo Pró-Saúde). Associações entre a 25(OH)D sérica e características sociodemográficas, consumo alimentar, uso de suplementos, atividade física, estação do ano na coleta da amostra de sangue, gordura corporal, fototipo de pele, índice de exposição solar e SNPs CYP2R1-rs10741657 e GC-rs2282679, explorados por regressão multilinear. A prevalência de 25(OH)D sérica < 50nmol/L foi 55%. A concentração sérica de 25(OH)D foi menor entre mulheres (β = -4,38; IC95%: -8,02; -0,74), indivíduos com mais gordura visceral (β = -4,02; IC95%: -5,92; -2,12) e genótipos AC e CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 e β = -10,63; IC95%: -17,52; -3,74, respectivamente). Os fatores associados diretamente à 25(OH)D sérica incluíram os meses de verão (β = 20,14; IC95%: 14,38; 25,90), fototipo intermediário (β = 6,16; IC95%: 2,52; 9,80), maior exposição solar (β = 0,49; IC95%: 0,22; 0,75), ingestão de vitamina D (β = 0,48; IC95%: 0,03; 0,93) e atividade física (β = 4,65; IC95%: 1,54; 7,76). Além de atividade física, dieta e exposição solar, fatores não modificáveis, tais como variantes do gene GC devem ser considerados na avaliação da deficiência de vitamina D em populações miscigenadas. Além disso, merece atenção a associação entre a gordura visceral elevada e o pior estado de vitamina D, uma vez que ambas as condições implicam em desfechos de saúde desfavoráveis, tanto crônicos quanto agudos.

Nuestro objetivo fue investigar factores asociados con la concentración sérica 25-hidroxivitamina D [25(OH)D] en adultos brasileños, considerando factores sociodemográficos y de vida, así como también los polimorfismos de nucleótido único relacionados con la vitamina D (SNPs). Se trata de un estudio transversal (n = 491; 34-79 años; 251 mujeres), anidado dentro de una cohorte prospectiva (Estudio Pro-Salud). Se investigaron las asociaciones entre concentración sérica 25(OH)D y características sociodemográficas, ingesta alimentaria, uso de suplementos, actividad física, estación del año de recogida de muestras de sangre, grasa corporal, tipo de piel, índice de exposición al sol, y SNPs CYP2R1-rs10741657 y GC-rs2282679 mediante una regresión múltiple lineal. La prevalencia sérica 25(OH)D < 50nmol/L fue 55%. La 25(OH)D sérica fue menor entre las mujeres (β = -4,38; IC95%: -8,02; -0,74), quienes tenían alta grasa visceral (β = -4,02; IC95%: -5,92; -2,12), genotipos AC y CC para GC-rs2282679 (β = -6,84; IC95%: -10,09; -3,59 y β = -10,63; IC95%: -17,52; -3,74, respectivamente). Los factores directamente asociados con la concentración sérica 25(OH)D incluyeron verano (β = 20,14; IC95%: 14,38; 25,90), tipo de piel intermedia (β = 6,16; IC95%: 2,52; 9,80), más alta exposición al sol (β = 0,49; IC95%: 0,22; 0,75), toma de vitamina D (β = 0,48; IC95%: 0,03; 0,93) y actividad física (β = 4,65; IC95%: 1,54; 7,76). Además de la actividad física, dieta y exposición al sol, los factores no modificables, tales como genotipos GC, necesitan tenerse en cuenta cuando se está evaluando la insuficiencia de vitamina D en poblaciones mestizas. Asimismo, las implicaciones de la asociación de una alta grasa visceral con un estatus más pobre de vitamina D merece que se le preste atención, puesto que ambas condiciones de salud están relacionadas desfavorablemente con resultados de salud graves y crónicos.

Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-γ genes and its association with susceptibility to tuberculosis: [review]

Mycobacterium tuberculosis kills more people than any other single pathogen, with an estimated one-third of the world's population being infected. Among those infected, only 10 percent will develop the disease. There are several demonstrations that susceptibility to tuberculosis is linked to host genetic factors in twins, family and associated-based case control studies. In the past years, there has been dramatic improvement in our understanding of the role of innate and adaptive immunity in the human host defense to tuberculosis. To date, attention has been paid to the role of genetic host and parasitic factors in tuberculosis pathogenesis mainly regarding innate and adaptive immune responses and their complex interactions. Many studies have focused on the candidate genes for tuberculosis susceptibility ranging from those expressed in several cells from the innate or adaptive immune system such as Toll-like receptors, cytokines (TNF-α, TGF-β, IFN-γ, IL-1b, IL-1RA, IL-12, IL-10), nitric oxide synthase and vitamin D, both nuclear receptors and their carrier, the vitamin D-binding protein (VDBP). The identification of possible genes that can promote resistance or susceptibility to tuberculosis could be the first step to understanding disease pathogenesis and can help to identify new tools for treatment and vaccine development. Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-γ genes, to generate resistance or susceptibility to M. tuberculosis infection.

Genetic Polymorphism of the Serum Proteins of Horses in Jeju

The study was carried out to investigate the genetic polymorphism of the serum proteins of horses in Cheju. They were assigned to three groups; 45 Cheju native horses(CNH), 60 Cheju racing horses(CRH) and 60 Thoroughbreds(TB). We analyzed the phenotypes and gene frequencies of serum proteins which were albumin (Alb), vitamin-D binding protein(GC), esterase (ES), A1B glycoprotein(A1B) and transferrin(TF) loci using horizontal polyacrylamide gel electrophoresis (HPAGE).All of the loci, except A1B in TB, showed polymorphisms and different allelic and phenotypic frequencies in all three groups. ESS and TFF1 were not observed in CNH. Allelic frequencies of AlbB, ESI, TFD and TFF1 were high in TB. All of the loci, except ES locus in CRH, appeared to be in a state of Hardy-Weinberg equilibrium from goodness-of-fit test in all three groups Heterozygosity estimates at Alb, ES and TF loci were high, but GC and A1B loci were low in all three groups. Average heterozygosities in CNH, CRH and TB were 0.3535, 0.3555 and 0.2726, respectively. Results showed differences in the frequencies of alleles and phenotypes of several serum protein loci between CNH and CRH, suggested that CRH might be crossed with other breeds of horses in some degree.

GC polymorphism investigated by isoelectric focusing: a study in south american indians

Os plasmas de um total de 488 indivíduos pertencentes a cinco populaçöes indígenas sul-americanas foram investigados, por meio de isoeletrofocalizaçäo, quanto ao sistema GC, e os resultados obtidos foram comparados aos descritos para onze outras tribos ameríndias. A um nível de 0,15 dissimilaridade genética foram observados quatro agrupamentos, näo tendo sido detectada uma associaçäo clara entre as freqüências alélicas neste sistema e a quantidade de radiaçäo solar