Genetic predisposition to salt-sensitive normotension and its effects on salt taste perception and intake (Genetics of salt sensitivity and salt intake)

Salt sensitivity is an independent CVD and mortality risk factor, which is present in both hypertensive and normotensive populations. It is genetically determined and it may affect the relationship between salt taste perception and salt intake. The aim of this study was to explore the genetic predisposition to salt sensitivity in a young and a middle-aged adult population and its effects on salt taste perception and salt intake. The effects of Na loading on blood pressure (BP) were investigated in twenty normotensive subjects and salt sensitivity defined as the change in BP after 7 d of low-Na (51·3 mmol Na/d) and 7 d of high-Na diet (307·8 mmol Na/d). Salt taste perception was identified using the British Standards Institution sensory analysis method (BS ISO 3972:2011). Salt intake was assessed with a validated FFQ. DNA was genotyped for SNP in the SLC4A5, SCNN1B and TRPV1 genes. The subjects with AA genotype of the SLC4A5 rs7571842 exhibited the highest increase in BP (∆ systolic BP=7·75 mmHg, P=0·002, d=2·4; ∆ diastolic BP=6·25 mmHg, P=0·044, d=1·3; ∆ mean arterial pressure=6·5 mmHg, P=0·014, d=1·7). The SLC4A5 rs10177833 was associated with salt intake (P=0·037), and there was an association between salt taste perception and salt sensitivity (rs 0·551, P=0·041). In conclusion, there is a genetic predisposition to salt sensitivity and it is associated with salt taste perception. The association between salt taste perception and discretionary salt use suggests that preference for salty taste may be a driver of salt intake in a healthy population and warrants further investigation

A systematic review of variations in circadian rhythm genes and type 2 diabetes.

Background: Type 2 diabetes (T2D) is a chronic disease that has severe individual and 26 societal consequences, which is forecast to worsen in future. A new field of investigation is 27 variations in circadian rhythm (CR) genes, in conjunction with diet and sleep variables, 28 associations with, and effects on, T2D development. 29 Objective: This systematic review aimed to analyse all current literature regarding CR gene 30 variations and T2D, and explore their interplay with diet and sleep variables on T2D 31 outcomes. This review was registered with PROSPERO (CRD42021259682). 32 Methodology: Embase and Pubmed were searched on 6/8/2021 / 11/8/2021 for studies of all 33 designs, including participants from both sexes, all ethnicities, ages, and geographic 34 locations. Participants with risk alleles / genotypes were compared with the wildtype 35 regarding T2D outcomes. Studies risk of bias were scored according to the ROBINS I/E 36 criteria. 37 Results: 31 studies were found (association n=29 / intervention n=2) including >600,000 38 participants from various ethnicities, sexes, and ages. Variations in the melatonin receptor 1b 39 (MTNR1B), brain and muscle arnt-like 1 (BMAL1) and period circadian regulator (PER) 40 genes were consistently associated with T2D outcomes. 41 Conclusions: Individuals with variations in MTNR1B, BMAL1 and PER may be at higher 42 risk of T2D. Further research is needed regarding other CR genes. More longitudinal studies 43 and randomised trials are required before clinical recommendations can be made

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 (CVD). Current dietary recommendations in the UK to reduce the risk of CVD 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

The associations between genetics, salt taste perception and salt intake in young adults

Food liking is one of the main determinants of food intake. Salt taste perception and preference, that play a role in liking of salt, may be genetically determined, although research in humans is scarce. The aim of this study was to explore the associations between genetics, salt taste perception, preference, self-reported salt habit and intake. The participants were young (18-35 years) and healthy adults (32 males and 63 females). Salt taste thresholds were determined with British Standard ISO3972:2011 methodology and salt taste preference by ratings of saltiness and pleasantness of tomato soup with salt concentrations reflecting salt content in foods. Self-reported salt habit was determined by asking participants how salty they usually eat their food and salt intake with two 24-hour 5-step multiple pass recalls. Genotyping for variants in the SCNN1B rs239345 and TRPV1 rs8065080 was performed. Participants homozygous for the minor allele of the rs8065080 had lower ratings of saltiness (p = 0.008) and higher ratings of pleasantness of soup (p = 0.027) when compared to major allele carriers. Preference for salt in soup was associated with salt habit (p = 0.003) and participants with high salt preference had higher salt intake compared to those with low salt preference (2236 ± 261 vs. 1543 ± 107 mg/1000 kcal, p = 0.017). TRPV1 rs8065080 may play a role in salt taste perception and preference, which should be confirmed in a larger sample size study. Hedonic appeal of salty food should be considered when providing personalised advice to change this behaviour

HIV-positive demonstrate more salt sensitivity and nocturnal non-dipping blood pressure than HIV-negative individuals

Background: High dietary salt and a lack of reduced blood pressure (BP) at night (non-dipping) are risk factors for the development of hypertension which may result in end-organ damage and death. The effect of high dietary salt on BP in black people of sub-Saharan Africa living with HIV is not well established. The goal of this study was to explore the associations between salt sensitivity and nocturnal blood pressure dipping according to HIV and hypertension status in a cohort of adult Zambian population. Methods: We conducted an interventional study among 43 HIV-positive and 42 HIV-negative adults matched for age and sex. Study participants were instructed to consume a low (4 g) dietary salt intake for a week followed by high (9 g) dietary salt intake for a week. Salt resistance and salt sensitivity were defined by a mean arterial pressure difference of ≤5 mmHg and ≥ 8 mmHg, respectively, between the last day of low and high dietary salt intervention. Nocturnal dipping was defined as a 10–15% decrease in night-time blood pressure measured with an ambulatory blood pressure monitor. Results: The median age was 40 years for both the HIV-positive and the HIV-negative group with 1:1 male to female ratio. HIV positive individuals with hypertension exhibited a higher BP sensitivity to salt (95%) and nondipping BP (86%) prevalence compared with the HIV negative hypertensive (71 and 67%), HIV positive (10 and 24%) and HIV-negative normotensive (29 and 52%) groups, respectively (p < 0.05). Salt sensitivity was associated with non-dipping BP and hypertension in both the HIV-positive and HIV-negative groups even after adjustment in multivariate logistic regression (< 0.001). Conclusions: The results of the present study suggest that high dietary salt intake raises blood pressure and worsens nocturnal BP dipping to a greater extent in hypertensive than normotensive individuals and that hypertensive individuals have higher dietary salt intake than their normotensive counterparts. Regarding HIV status, BP of HIV-positive hypertensive patients may be more sensitive to salt intake and demonstrate more non-dipping pattern compared to HIV-negative hypertensive group. However, further studies with a larger sample size are required to validate this

Immediate pressor response to oral salt and its assessment in the clinic: a time series clinical trial

Background: High blood pressure (BP) is associated with high-salt consumption especially in sub-Saharan Africa. Although the pressor efect of salt is viewed as a chronic efect, some studies suggest that a salty meal may increase BP immediately in some individuals, and that this efect may cause endothelial dysfunction. Therefore, the aim of our research was to study the immediate pressor response to oral salt (IPROS) and its determinants, with the expectation that a simple methodology may be devised to diagnose it in the clinic or in low-resource environments. Methods: We conducted a time series trial at Livingstone Central Hospital. We present data in 127 normotensive participants who ingested 2g of sodium chloride; their BP was monitored for 120minutes in intervals of 10minutes. Sociodemographic and clinical data were collected. Descriptive and inferential statistics were used for analyses of data. Results: Median age was 30 years (interquartile range, 22–46 years) and 52% were female patients. An increase of ≥10mmHg in mean arterial pressure (MAP), considered a clinically signifcant IPROS, was present in 62% of participants. Systolic BP 30minutes after the salt load was a signifcant predictor of IPROS, avoiding the need to calculate MAP in the clinic setting. Conclusions: We confrm the presence of an IPROS in a high proportion (62%) of otherwise normotensive participants. The average time course for this response was 30minutes and its duration was sustained for the 120-minutes period of study in most of the participants. Prediction of IPROS by ∆SBP (change in systolic blood pressure) at 30minutes allows for easy assessment of possible responder status in the clinic. Our data indicate that the IPROS to oral saltloads in the range currently consumed by the Western world and African populations in single meals may increase the 24-hour BP load, which is a risk factor for hypertension and target organ damage. The relevance of our fndings indicates the need to include dietary sodium assessment in the diagnosis, prevention, and management of high BP

Genetic differences in fat taste sensitivity and dietary intake in a UK female cohort

Over the past decade, a potential sixth taste, fat taste (“oleogustus”), has been identified. Studies in adults and children of various ethnicities have demonstrated that both lifestyle and genetic factors may contribute to fat taste sensitivity (FTS). Data on females in the UK is limited. The aim of this study was to determine, using an ethnically similar, healthy, female cohort, whether known genotypes related to fat taste and dietary intake lead to differences in FTS. A cross-sectional study was carried out on a UK cohort of Caucasian females (32.7 ± 11.4 years, 23.7 ± 3.6 kg/m2). We report that FTS differed in individuals with differing genotypes; genotypes that have previously been associated with differences in dietary intake. Specifically, FTS was lower in rs1514175 Troponin I-Interacting Protein Kinase (TNNI3K) gene AA/AG genotype and was higher in rs6265 Brain Derived Neurotrophic Factor (BDNF) gene TT/CT genotype (both p < 0.05). We also report that participants in the rs1514175 TNNI3K AA/AG genotype group had a higher energy intake, total fat intake, and subsequently, higher monounsaturated fat and saturated fat intake when compared to the GG genotype (all p < 0.05). To our knowledge, this is the first study showing associations between genotypes that have been previously associated to dietary intake are also associated to FTS. Due to the heterogeneity of previous research and the infancy of fat taste research, further research is required on a larger, ethnically similar cohort

The associations between bitter and fat taste sensitivity, and dietary fat intake: Are they impacted by genetic predisposition?

A relationship between bitter and fat taste sensitivity, CD36 rs1761667 and TAS2R38 has been demonstrated. However, research is scarce and does not take diet into account. This study aimed to explore associations between genetics, fat and bitter taste sensitivity and dietary fat intake in healthy UK adults. A cross-sectional study was carried out on 88 Caucasian participants (49 females and 39 males aged 35 ± 1 years; body mass index 24.9 ± 0.5 kg/m 2). Bitter taste sensitivity was assessed using phenylthiocarbamide (PTC) impregnated strips and the general Labelled Magnitude Scale. Fat taste sensitivity was assessed by the Ascending Forced Choice Triangle Procedure and dietary intake with a semi-quantitative food frequency questionnaire. Genotyping for rs713598, rs1726866, rs10246939 and rs1761667 was performed. Participants with TAS2R38 PAV/PAV diplotype perceived PTC strips as more bitter than groups carrying AVI haplotypes (AVI/AVI, p = 1x10 -6; AVI/AAV, p = 0.029). CD36 rs1761667 was associated with fat taste sensitivity (p = 0.008). A negative correlation between bitter taste sensitivity and saturated fat intake was observed (rs = -0.256, p = 0.016). When combining the CD36 genotypes and TAS2R38 diplotypes into one variable, participants carrying both TAS2R38 AVI haplotype and CD36 A allele had a higher intake of saturated fat compared to carriers of CD36 GG genotype or TAS2R38 PAV/PAV and PAV/AAV diplotypes (13.8 ± 0.3 vs 12.6 ± 0.5 %TEI, p = 0.047) warranting further exploration in a larger cohort