Host genetic factors determining COVID-19 susceptibility and severity.

Genome-wide single nucleotide polymorphism (SNP) data are now quickly and inexpensively acquired, raising the prospect of creating personalized dietary recommendations based on an individual’s genetic variability at multiple SNPs. However, relatively little is known about most specific gene–diet interactions, and many molecular and clinical phenotypes of interest (e.g., body mass index [BMI]) involve multiple genes. In this review, we discuss direct to consumer genetic testing (DTC-GT) and the current potential for precision nutrition based on an individual’s genetic data. We review important issues such as dietary exposure and genetic architecture addressing the concepts of penetrance, pleiotropy, epistasis, polygenicity, and epigenetics. More specifically, we discuss how they complicate using genotypic data to predict phenotypes as well as response to dietary interventions. Then, several examples (including caffeine sensitivity, alcohol dependence, non-alcoholic fatty liver disease, obesity/appetite, cardiovascular, Alzheimer’s disease, folate metabolism, long-chain fatty acid biosynthesis, and vitamin D metabolism) are provided illustrating how genotypic information could be used to inform nutritional recommendations. We conclude by examining ethical considerations and practical applications for using genetic information to inform dietary choices and the future role genetics may play in adopting changes beyond population-wide healthy eating guidelines.

Genomics in Personalized Nutrition: Can You "Eat for Your Genes"?

In humans the ability to digest milk lactose is conferred by a β-galactosidase enzyme called lactase-phlorizin hydrolase (LPH). While in some humans (approximately two-thirds of humankind) the levels of this enzyme decline drastically after the weaning phase (a trait known as lactase non-persistence (LNP)), some other individuals are capable of maintaining high levels of LPH lifelong (lactase persistence (LP)), thus being able to digest milk during adulthood. Both lactase phenotypes in humans present a complex genetic basis and have been widely investigated during the last decades. The distribution of lactase phenotypes and their associated single nucleotide polymorphisms (SNPs) across human populations has also been extensively studied, though not recently reviewed. All available information has always been presented in the form of static world maps or large dimension tables, so that it would benefit from the newly available visualization tools, such as interactive world maps. Taking all this into consideration, the aims of the present review were: (1) to gather and summarize all available information on LNP and LP genetic mechanisms and evolutionary adaptation theories, and (2) to create online interactive world maps, including all LP phenotype and genotype frequency data reported to date. As a result, we have created two online interactive resources, which constitute an upgrade over previously published static world maps, and allow users a personalized data exploration, while at the same time accessing complete reports by population or ethnicity.

https://www.mdpi.com/2072-6643/12/9/2689/pdf

Genetics of Lactose Intolerance: An Updated Review and Online Interactive World Maps of Phenotype and Genotype Frequencies.

OBJECTIVES: The aim of the study was to characterize the microbiota profiles of patients with Hirschsprung disease (HD) and to evaluate this in relation to postoperative bowel function and the incidence of Hirschsprung-associated enterocolitis (HAEC). METHODS: All patients operated on for HD at our center between 1987 and 2011 were invited to answer questionnaires on bowel function and to participate in a clinical follow-up for laboratory investigations, including fecal DNA extraction, fecal calprotectin (FC), and brush border lactase (LCT) genotyping. The microbiota compositions of patients with HD were compared with those of healthy controls aged between 2 and 7 years. RESULTS: The microbiota composition of eligible patients with HD (n = 34; median age 12 [range, 3-25] years) differed from the healthy controls (n = 141), showing decreased overall microbial richness (P < 0.005). Seventy-seven percent had experienced HAEC. Normal maturation of the intestinal flora was not observed, but patients had a significantly increased abundance of Proteobacteria among other taxa (P < 0.005) resulting in a reduced carbohydrate degradation potential, as predicted by the taxonomic composition. Genetic lactase deficiency was present in 17% and did not correlate with bowel symptoms. No patients reported active HAEC at the time of sampling and FC was within the normal range in all samples. CONCLUSIONS: Patients with HD and HAEC had a significantly altered intestinal microbiome compared to healthy individuals, characterized by a lack of richness and pathologic expansions of taxa, particularly Enterobacteria and Bacilli. Further evaluation is needed to identify whether these observations are intrinsic to HD or secondary to the recurrent use of antibiotics during early childhood.

/pdf/intestinal-microbiota-in-hirschsprung-disease-icmykvxkxh.pdf

Intestinal Microbiota in Hirschsprung Disease.

Novel coronavirus disease 2019 (COVID‐19) poses a global threat, due to its fluctuating frequency and lethality. Published data revealed associations of COVID‐19 susceptibility and severity with host genetic polymorphisms in renin‐angiotensin‐aldosterone system (RAAS)‐related genes including angiotensin‐converting enzyme (ACE)1, ACE2, and transmembrane protease (TMPRSS)2. However, the findings remain inconclusive. Accordingly, we aimed to clarify associations of genetic variants in those genes with COVID‐19 susceptibility and severity using a systematic review with meta‐analysis. From inception through 1 July 2021, a literature search was performed using PubMed, Scopus, Web of Science, and Cochrane Library databases. Allelic distributions for each polymorphism were calculated as pooled odds ratios (OR) with 95% confidence intervals (CI) to assess the strength of association. A total of 3333 COVID‐19 patients and 5547 controls from 11 eligible studies were included. From a systematic review, ACE1 rs1799752, ACE1 rs4646994, ACE2 rs2285666, and TMPRSS2 rs12329760 were identified as common polymorphisms of RAAS‐related genes. Meta‐analysis showed a significant association between TMPRSS2 rs12329760 C‐allele and an increased risk of developing severe COVID‐19 (OR = 1.32, 95% CI: 1.01, 1.73). Likewise, additional meta‐analyses uncovered that both ACE1 rs4646994 DD‐genotype and ACE2 rs2285666 GG‐genotype carriers had a significantly increased risk of developing severe COVID‐19 (OR = 2.06, 95% CI: 1.45, 2.93; OR = 2.14, 95% CI: 1.26, 3.66; respectively). Genetic polymorphisms of ACE1 rs4646994 DD‐genotype, ACE2 rs2285666 GG‐genotype, and TMPRSS2 rs12329760 CC‐genotype and C‐allele may serve as predictive models of COVID‐19 severity.

Genetic polymorphisms of ACE1, ACE2, and TMPRSS2 associated with COVID‐19 severity: A systematic review with meta‐analysis

ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors.

Infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease (COVID-19), has spread widely around the globe. Significant inter-individual differences have been observed during the course of the infection, which suggests that genetic susceptibility may be a contributing factor. CC chemokine receptor 5 (CCR5), which acts as a co-receptor for the entry of HIV-1 into cells, is promising candidate whose can have an influence on SARS-CoV-2 infection. A genetic mutation known as CCR5Delta32, consisting of a 32-nucleotide deletion, encodes a truncated protein that protects homozygous carriers of the deletion from HIV-1 infection. Similarly, inhibition of CCR5 seems to be protective against COVID-19. In our study, we successfully genotyped 416 first-wave SARS-CoV-2-positive infection survivors (164 asymptomatic and 252 symptomatic) for CCR5?32, comparing them with a population based sample of 2,404 subjects. We found the highest number (P=0.03) of CCR5Delta32 carriers in SARS-CoV-2-positive/COVID-19-asympto-matic subjects (23.8 %) and the lowest number in SARS-CoV-2-positive/COVID-19-symptomatic patients (16.7 %), with frequency in the control population in the middle (21.0 %). We conclude that the CCR5?32 I/D polymorphism may have the potential to predict the severity of SARS-CoV-2 infection.

/pdf/ccr5delta32-deletion-as-a-protective-factor-in-czech-first-344e30r5sc.pdf

CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects

Lactase non-persistence (leading to primary lactose intolerance) is a genetically dependent inability to digest lactose in adulthood. As part of the human adaptation to dairying, the human lactase LCT-13910C/T mutation (which propagates adult expression of lactase) developed, spread and participated in the adaptation to dairying. This variant is associated with lactase activity persistence, and its carriers are able to digest lactose. We compared the frequencies of lactase 13910C/T (rs4988235) genotypes in Czechs/Slavs (N = 288) and Czech Gypsies/Roma (N = 300), two ethnically different groups where this polymorphism has not yet been analysed. Allelic frequencies significantly differed between the populations (p < 0.0001). In Czechs/Slavs, the lactase persistence T allele was present in 76% of the individuals, which is in agreement with frequencies among geographically neighbouring populations. In the Czech Gypsy/Roma population, only 27% of the adults were carriers of at least one lactase persistence allele, similar to the Indian population. In agreement with this result, dairy product consumption was reported by 70.5% of Czechs/Slavs and 39.0% of the Czech Gypsy/Roma population. Both in the Czech Gypsy/Roma and in the Czech/Slavs populations, the presence of carriers of the lactase persistence allele was similar in subjects self-reporting the consumption of unfermented/fresh milk, in comparison to the others.

/pdf/frequency-of-adult-type-associated-lactase-persistence-lct-15fl9pfko7.pdf

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations.

Our previous study showed that a diet enriched with 400 g of carp per week improved plasma lipids in subjects after aortocoronary bypass (CABG). The aim of the present study is to determine whether the different carp farming systems have an impact on the effects of carp meat in secondary cardiovascular prevention. We examined 3 groups of patients after CABG over a 4-week period of spa treatment (108 persons, 73 males, 35 females, age over 60 years). We found no differences in baseline values of blood pressure or plasma lipids. The patients were given a standard spa diet (controls; N=36) or a diet enriched of 400 g of carp meat per week, enriched omega 3 (N=37) or cereal carp (N=35). Plasma lipid parameters were examined at start and after 4 weeks in a routine laboratory setting. Group consuming omega-3 carp showed the largest decline in total cholesterol, LDL cholesterol, triglycerides and an increase in HDL cholesterol (all p<0.01). We found that carp meat from the two production systems showed significantly different effects on plasma lipids. Further trials should be performed to clarify the exact causes of the differences.

/pdf/intake-of-carp-meat-from-two-aquaculture-production-systems-eviini7xxq.pdf

Intake of carp meat from two aquaculture production systems aimed at secondary prevention of ischemic heart disease - a follow-up study.

Objective: The aim of the study was to analyse the frequencies of rs1229984 genotypes within the alcohol dehydrogenase (ADH1B) gene in a Gypsies/Roma population and compare them with other populations and with ethanol consumption.
Methods: We analysed the ADH1B (rs1229984; Arg47→His; c.143G>A) genotype using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) in two ethnically different groups - Gypsies/Roma (N = 301) and Czechs (N = 300) where one day alcohol consumption was recorded.
Results: ADH1B genotype/allelic frequencies did not significantly differ between the populations (p = 0.32). The frequency of minor A allele carriers was slightly higher in Gypsies/Roma (14.7%) than in Czechs (11.9%). The prevalence of subjects reporting alcohol intake on the previous day was non-significantly lower in Gypsies/Roma (10.5% vs. 16.4%), as was the amount of alcohol consumed the day before the examination in ethanol consumers (36.1 ± 18.3 g vs. 43.0 ± 27.2 g).
Conclusions: The frequency of rs1229984 genotypes in the ADH1B gene within the Gypsies/Roma population corresponds with frequencies obtained in North India/Central Asia, the putative country of this ethnic origin. Our results suggest that the minority Gypsies/Roma population consume slightly less alcohol than the Czech majority population.

/pdf/distribution-of-adh1b-genotypes-predisposed-to-enhanced-2x5x9flkz2.pdf

Vaclav Adamek

Papers

ACE I/D polymorphism in Czech first-wave SARS-CoV-2-positive survivors.

CCR5Delta32 deletion as a protective factor in Czech first-wave COVID-19 subjects

Frequency of adult type-associated lactase persistence LCT-13910C/T genotypes in the Czech/Slav and Czech Roma/Gypsy populations.

Intake of carp meat from two aquaculture production systems aimed at secondary prevention of ischemic heart disease - a follow-up study.

Distribution of ADH1B genotypes predisposed to enhanced alcohol consumption in the Czech Roma/Gypsy population.