Effects of CYP3A4*22 polymorphism on trough concentration of tacrolimus in kidney transplantation: a systematic review and meta-analysis.

Purpose: Tacrolimus (Tac) is a widely used immunosuppressive agent in kidney transplantation. Cytochrome P450 (CYP), especially CYP3A4 enzymes are responsible for the metabolism of drugs. However, the correlation between plasma Tac concentration and CYP3A4*22 gene variants is controversial. This meta-analysis aims to evaluate the association between CYP3A4*22 polymorphism and the dose-adjusted trough concentration (C0/D) of Tac in adult kidney transplant patients. Methods: We conducted a literature review for qualifying studies using the PubMed, Web of Science, and Embase databases until July 2023. For the continuous variables (C0/D and daily dose), mean difference (MD) and corresponding 95% confidence intervals (CIs) were calculated to evaluate the association between the CYP3A4 * 22 and Tac pharmacokinetics. We performed an additional analysis on the relationship of CYP3A5*3 with Tac PKs and analyzed the effects of CYP3A4*22 in CYP3A5 non-expressers. Results: Overall, eight eligible studies with 2,683 renal transplant recipients were included in this meta-analysis. The CYP3A4*22 allele was significantly associated with a higher C0/D (MD 0.57 ng/mL/mg (95% CI: 0.28 to 0.86; p = 0.0001) and lower mean daily dose requirement (MD -2.02 mg/day, 95% CI: -2.55 to -1.50; p < 0.00001). An additional meta-analysis demonstrated that carrying the CYP3A5*3 polymorphism greatly impacted Tac blood concentration. From the result with CYP3A5 non-expressers, CYP3A4*22 showed significant effects on the Tac C0/D and dose requirement even after adjusting the effect of CYP3A5*3. Conclusion: Patients with CYP3A4*22 allele showed significantly higher plasma C0/D of Tac and required lower daily dose to achieve the therapeutic trough level after kidney transplantation. These findings of our meta-analysis may provide further evidence for the effects of genetic polymorphism in CYP3A4 on the PKs of Tac, which will improve individualized treatment in a clinical setting.

Association between ABCA1 Gene Polymorphisms and Plasma Lipid Concentration: A Systematic Review and Meta-Analysis.

BACKGROUND: Although ABCA1 gene polymorphisms may be associated with the plasma lipid concentration, the literature has not shown a consistent pattern. In this study, we attempted to elucidate the association between the ABCA1 69C>T, 825V>I, and 230R>C polymorphisms and the plasma lipid concentration through a systematic review and meta-analysis. METHODS: We selected studies published up to October 2020 in the PubMed, Web of Science, and Embase databases according to inclusion and exclusion criteria. The mean difference (MD) and 95% confidence interval (CI) were used to assess the relationship between the presence of ABCA1 69C>T, 825V>I, and 230R>C and plasma lipid levels. Meta-analysis was performed using Review Manager (version 5.3). Both Begg's test and Egger's regression test of the funnel plot were performed using R Studio software (version 3.6.0) to identify publication bias. RESULTS: We analyzed the data on the ABCA1 69C>T polymorphism involving 14,843 subjects in 11 studies, 825V>I polymorphism involving 2580 subjects in 5 studies, and 230R>C polymorphism involving 4834 subjects in 4 studies. The T allele carriers in 69C>T, II carriers in 825V>I, and C carriers in 230R>C had lower high-density lipoprotein cholesterol levels; the MD (95% CI) was -0.05 mmol/L (95% CI: -0.09 to -0.01, p = 0.02), -0.05 mmol/L (95% CI: -0.09 to -0.00, p = 0.03), and -0.1 mmol/mL (95% CI: -0.12 to -0.07 mmol/L, p < 0.00001), respectively. In the case of 230R>C, the serum total cholesterol concentration of C carriers was significantly lower than that of RR carriers (-0.2 mmol/L, 95% CI: -0.3 to -0.11, p < 0.0001). CONCLUSION: This meta-analysis demonstrates that the ABCA1 69C>T, 825V>I, and 230R>C polymorphisms could affect the plasma lipid concentration. As the plasma lipid concentration may be related to various diseases, ABCA1 genotyping could be useful for the management of lipid levels.

Socioeconomic Characteristics and Trends in the Consumption of Ultra-Processed Foods in Korea from 2010 to 2018.

There is growing evidence for a global transition to a more highly processed diet. While the dietary share of ultra-processed foods depends on a country's economic status, food choice and consumption are also influenced by the socioeconomic situation of individuals. This study investigated whether ultra-processed food consumption differed across socioeconomic subgroups and over time (2010-2018) in Korea. Cross-sectional data from the Korea National Health and Nutrition Examination Survey 2010-2018 were analyzed. Food and beverages reported in a one-day 24 h recall were classified according to the NOVA food classification criteria. The dietary energy contribution of ultra-processed foods was high among men and urban residents, and increased with education and income level; additionally, it reached its peak in adolescents and thereafter decreased with increasing age. After adjusting the socioeconomic variables, such associations remained significant, except for income level. The overall contribution of ultra-processed foods increased from 23.1% (2010-2012) to 26.1% (2016-2018), and the same trend over time was observed in all age groups and socioeconomic strata. In the Korean population, ultra-processed food consumption differed by individual socioeconomic characteristics, but gradually increased over time, and this trend was consistently found in all socioeconomic subgroups. Future strategies to promote healthy food choices are needed for the Korean population.

Association between serum 25-hydroxyvitamin D levels and pulmonary function, among Korean adults, during 2010-2014, by sex, age, and body mass index.

BACKGROUND: This study examined the association between serum 25-hydroxyvitamin D (25(OH)D) and pulmonary function, among Korean adults, from 2010 to 2014. METHODS: The data were obtained from the fifth Korea National Health and Nutrition Examination Survey (KNHANES 5), and the first and second year (2013-2014) of KNHANES 6. The study population comprised 14,378 individuals. The variable of interest was serum 25(OH)D, and the dependent variable, pulmonary function. RESULTS: All people with vitamin D levels below 30 ng/ml had lower lung functions, which was significant in lower forced expiratory volume in the first second (FEV1) (serum 25(OH)D < 10 ng/ml, 20 to <30 ng/ml: P = .001, 10 to <20 ng/ml: P = 0) and forced vital capacity (FVC) (serum 25(OH)D level <10 ng/ml: P = .01, 10 to < 20 ng/ml: P = .001, 20 to <30 ng/ml: P = .008). The lower the serum 25(OH)D, the lower the levels of FEV1 in men and this was significant. (serum 25(OH)D < 10 ng/ml: P = .007, 10 to <20 ng/ml: P = .002, 20 to <30 ng/ml: P = .007). The values of FEV1 and FVC were lower in people aged 50-69 years when vitamin D was lower than 30 ng/ml which were all significant. Among participants with BMI values < 23 kg/m2, lower vitamin D levels were significantly associated with lower pulmonary function. CONCLUSIONS: We found a significant association between serum 25(OH)D and pulmonary function, and this was related to sex, age and body mass index.