Does personalised nutrition advice based on apolipoprotein E and methylenetetrahydrofolate reductase genotype affect dietary behaviour?

Background: Dietary intake is linked to numerous modifiable risk factors of cardiovascular disease. Current dietary recommendations in the UK to reduce the risk of cardiovascular disease are not being met. A genotype-based personalised approach to dietary recommendations may motivate individuals to make positive changes in their dietary behaviour. Aim: To determine the effect of a personalised nutrition intervention, based on apolipoprotein E ( ApoE, rs7412; rs429358) and methylenetetrahydrofolate reductase ( MTHFR, rs1801133) genotype, on reported dietary intake of saturated fat and folate in participants informed of a risk genotype compared to those informed of non-risk genotype. Methods: Baseline data ( n = 99) were collected to determine genotype (non-risk vs risk), dietary intake and cardiovascular risk (Q-Risk®2 cardiovascular risk calculator). Participants were provided with personalised nutrition advice via email based on their ApoE and MTHFR genotype and reported intake of folate and saturated fat. After 10 days, dietary intake data were reported for a second time. Results: Personalised nutrition advice led to favourable dietary changes, irrespective of genotype, in participants who were not meeting dietary recommendations at baseline for saturated fat ( p < 0.001) and folate ( p = 0.002). Only participants who were informed of a risk ApoE genotype met saturated fat recommendations following personalised nutrition advice. Conclusion: Incorporation of genotype-based personalised nutrition advice in a diet behaviour intervention may elicit favourable changes in dietary behaviour in participants informed of a risk genotype. Participants informed of a non-risk genotype also respond to personalised nutrition advice favourably but to a lesser extent.

Asparaginase Induced Liver Enzyme Elevation Is More Prevalent in Hispanics Children with ALL and in Patients with SOD2 rs4880 CC Genotype

Background: Asparaginase is an integral component of treatment for pediatric patients with acute lymphoblastic leukemia (ALL). Hepatotoxicity secondary to asparaginase-based treatment is one of the most common treatment-related toxicities in ALL therapy. Hispanic children are at higher risk of ALL and ALL treatment related toxicities compared with other ethnicities. The rs4880 variant in the SOD2 gene, a critical mitochondrial enzyme that protects cells against oxidative stress, was previously found to be associated with increased incidence of hepatotoxicity following asparaginase treatment in an adult ALL cohort of largely European ancestry. Whether this association is also present in pediatric patients with ALL and in Hispanics remains unknown. Importantly, the risk genotype (CC) of rs4880 is more frequent among Hispanics. Here we aim to investigate the prevalence of hepatotoxicity and risk genotype among pediatric patients with ALL particularly of Hispanics ancestry. Method: Blood samples, demographic and clinical data were obtained from 143 pediatric patients treated for ALL between 29 January 2015 and 24 January 2020 at Children's Hospital Los Angeles. We genotyped DNA samples isolated from the patient's blood for the rs4880 variant of SOD2 using TaqMan Allelic Discrimination Assay. Liver enzyme data, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin levels for each subject following multiple visits before and post asparaginase-based treatment were obtained. Hepatotoxicity is defined as grade 3/4 of both AST and ALT, grade 4 of either AST or ALT, or grade 3/4 of bilirubin. We performed Cox Proportional Hazards models to evaluate the predictive factors of hepatotoxicity overtime. Results: Among the 143 patients, 13 (9.09%) patients had grade &gt; 3 elevated bilirubin levels, and 3 (2.1%) and 55 (38.46%) patients had grade &gt; 4 and &gt; 3 elevated AST levels respectively, and 19 (13.29%) and 109 (76.22%) had grade &gt; 4 and &gt; 3 elevated ALT levels respectively. Hepatotoxicity was observed in 60 (41.96%) of patients. After dichotomizing patients based on ethnicity (Hispanic and non-Hispanic), we found that BMI was significantly higher in Hispanics than non-Hispanic patients (mean BMI: 21.57 vs 18.64, p=0.002). While mean baseline levels of liver enzymes were not significantly different between Hispanic and non-Hispanic patients (bilirubin:0.69 vs 0.64, ALT: 156.06 vs 124.75, and AST: 99.98 vs 82.38), post-treatment levels were significantly higher in hispanics (ALT: 138.105 vs. 101.45, p=0.0005; AST: 84.131 vs. 64.045, p=0.0023). After chemotherapy, grade 3 or 4 elevated bilirubin was found in 11 (12.36%) of 89 Hispanic patients and only in 2 (3.7%) of 54 non-Hispanic patients. Also, there was a statistically significant difference in the frequency of elevated ALT level grade &gt; 4 and grade &gt; 3 between Hispanic and non-Hispanic patients (grade &gt; 4: 17 (19.10%) vs 2 (3.70), p= 0.01; grade &gt; 3: 74 (83.15%) vs 35 (64.8%), p=0.01). Consequently, Hepatotoxicity was more frequent among Hispanic patients than non-Hispanic, 47.19% vs 33.33%; p=0.10, respectively. We also compared hepatotoxicity parameters according to the patient's rs4880 genotypes. Among patients with the SOD2 rs4880 CC genotype 3 (6.32%) had grade &gt; 4 and 23 (50%) had grade &gt; 3 elevated AST compared with 0 (0%) and 21 (30%) among the CT and 0 (0%) and 11 (40.74%) among the TT genotype patients (CC vs. CT and TT; AST grade &gt; 4: p=0.13; grade &gt; 3 : p=0.05). In addition, elevated bilirubin grade &gt; 3 was found more frequently in patients with the SOD2 rs4880 CC genotype (15.22%) compared with those with the CT (5.71%) and TT (7.41%) genotypes. Furthermore, post-treatment bilirubin, ALT and AST median levels were significantly higher in patients with the CC genotype than in patients with CT or TT genotypes (bilirubin: 0.8275 vs. 0.6, p=0.0007; ALT: 142.555 vs. 106.038, p=0.0089; AST: 85.399 vs. 67.888, p= 0.0302). In a multivariate Cox analysis, that included ethnicity, age, gender, BMI and genotype, we identified Ethnicity (Hispanic) as the only significant predictor of hepatotoxicity (hazard ratio [HR] = 1.862, 95% confidence interval [95% CI] 1.-3.465, p=0.0499). Conclusion: Overall, these findings suggested that hepatotoxicity is highly prevalent among Hispanic pediatric patients with ALL, especially those with CC genotype of rs4880. Disclosures Stock: Pfizer: Consultancy, Honoraria, Research Funding; amgen: Honoraria; agios: Honoraria; jazz: Honoraria; kura: Honoraria; kite: Honoraria; morphosys: Honoraria; servier: Honoraria; syndax: Consultancy, Honoraria; Pluristeem: Consultancy, Honoraria.

Il-18 Overproduction Associated with NLRP1 Single Nucleotide Polymorphisms Linked to Risk for Vitiligo

Background The NLRP1gene is central to the NLR inflammasome. Variants to the NLRP1 gene are associated with vitiligo and other autoimmune diseases. We examined the effects of two single nucleotide polymorphisms (SNP) son cytokine levels and NLRP1 gene expression in 50 human volunteers. Methods NLRP1 was genotyped at SNPs rs2670660 and rs12150220, and participants who were homozygous at one or more SNP were analyzed. Plasma IL-18 and IL-1β levels were quantified using ELISA. NLRP1 gene expression was measured using real-time PCR. Results Participants with the risk genotype had significantly higher levels of plasma IL-18 than participants with protective genotype (0.439 ng/µL compared to 0.152 ng/µL, p = 0.024). Genotypes rs2670660 and rs12150220 were strongly linked in this population (p = 2.33 x 10-13). Conclusions Increased production of IL-18, suggests that at least one of the AA variants of rs2670660 or rs12150220 increases NLRP1 activity. rs2670660 and rs12150220 are strongly linked.