Sarabjit Mastana | Loughborough University (original) (raw)

Papers by Sarabjit Mastana

Elsevier eBooks, 2021

Abstract Nutri-epigenomics seeks to delineate the interactions between the diet and the genome th... more Abstract Nutri-epigenomics seeks to delineate the interactions between the diet and the genome through epigenetic mechanisms. The ability of the epigenome to adapt to environmental factors, including diet, is referred to as “plasticity” and this alters across the lifespan of an organism. Thus, there are periods during which the epigenome is more responsive to change (Kanherkar et al., 2014), for example, increased plasticity occurs in prenatal and neonatal phases, when cell differentiation and specialization is taking place. Environmental factors, such as nutrition, therefore, have more influence during these periods of development. Sometimes the epigenetic consequences can be quite dramatic, for example, when genetically identical larvae of the honeybee are fed royal jelly, the DNA methylation patterns are altered, resulting in differentiation into a Queen bee rather than a worker bee (Kucharski et al., 2008). In mammals, malnutrition of methyl donors vitamin B12 and choline during gestation can lead to epigenetic dysregulation within the offspring, giving rise to obesity and influencing disease in later life (Waterland and Jirtle, 2003).

Journal of Nutrition, Jul 1, 2019

Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly w... more Background: After meal ingestion, a series of coordinated hormone responses occur concomitantly with changes in perceived appetite. It is not known whether interindividual variability in appetite exists in response to a meal. Objectives: The aim of this study was to 1) assess the reproducibility of appetite responses to a meal; 2) quantify individual differences in responses; and 3) explore any moderating influence of the fat mass and obesity associated (FTO) gene. Methods: Using a replicated crossover design, 18 healthy men (mean ± SD age: 28.5 ± 9.8 y; BMI: 27.0 ± 5.0 kg/m 2) recruited according to FTO genotype (9 AA, 9 TT) completed 2 identical control and 2 identical standardized meal conditions (5025 kJ) in randomized sequences. Perceived appetite and plasma acylated ghrelin, total peptide YY (PYY), insulin, and glucose concentrations were measured before and after interventions as primary outcomes. Interindividual differences were explored using Pearson's product-moment correlations between the first and second replicates of the control-adjusted meal response. Within-participant covariate-adjusted linear mixed models were used to quantify participant-by-condition and genotype-by-condition interactions. Results: The meal suppressed acylated ghrelin and appetite perceptions [standardized effect size (ES): 0.18-4.26] and elevated total PYY, insulin, and glucose (ES: 1.96-21.60). For all variables, SD of change scores was greater in the meal than in the control conditions. Moderate-to-large positive correlations were observed between the 2 replicates of controladjusted meal responses for all variables (r = 0.44-0.86, P ≤ 0.070). Participant-by-condition interactions were present for all variables (P ≤ 0.056). FTO genotype-by-condition interactions were nonsignificant (P ≥ 0.19) and treatment effect differences between genotype groups were small (ES ≤ 0.27) for all appetite parameters. Conclusions: Reproducibility of postprandial appetite responses is generally good. True interindividual variability is present beyond any random within-subject variation in healthy men but we detected no moderation by the FTO genotype. These findings highlight the importance of exploring individual differences in appetite for the prevention and treatment of obesity. This trial was registered at clinicaltrials.gov as NCT03771690.

Recently atherosclerosis and coronary artery disease (CAD) are considered to be inflammatory dise... more Recently atherosclerosis and coronary artery disease (CAD) are considered to be inflammatory diseases. The genetic polymorphism in inflammatory markers has been well studied and found to be associated with development of CAD. To study the association of biallelic polymorphism at position 196 in exon 6 of tumor necrosis factor 2 (TNFR2) gene and coronary artery disease. The study design was a prospective case control study conducted at a tertiary referral center mainly catering to the north Indian population. One hundred and fifty angiographically proven patients with coronary artery disease and one hundred and fifty age matched controls were genotyped for TNFR2 gene by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. Genotype frequencies were compared in patients and controls by Chi-square test. Binary logistic regression analysis was used to examine the relationship between genotypes and disease, incorporating other variables into the model. The incidence of CAD in those with MM genotype was 65% and in those with RM genotype was 42%. Genotype frequency shows significant association of MM genotype with development of CAD (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001; odds ratio-2.585; 95% confidence interval 1.533-4.359). The association of TNFR2 genotype with CAD persisted on logistic regression analysis. MM genotype of TNFR2 gene is associated with development of CAD and RM genotype appears to be protective.

PubMed, Oct 1, 1996

HLA-DR and HLA-DQ allele frequencies in four populations (Brahmin, Maratha, Gujarati Hindu Patel,... more HLA-DR and HLA-DQ allele frequencies in four populations (Brahmin, Maratha, Gujarati Hindu Patel, and Parsi) of Bombay, western India, were analyzed using TaqI RFLPs detected by the cDNA probes DRB, DQB, and DQA. Although the overall differences in the HLA-DR and HLA-DQ genotype frequencies among the populations were not statistically significant, several population-specific haplotypes were significant. Multivariate analyses using data on 2 loci (HLA-DR and HLA-DQ) produced a meaningful pattern of genetic affinity and differentiation that parallels the analysis made when frequency data on 23 loci (21 blood group and protein loci and 2 class II antigen loci) are used. The RST for class II loci was 0.006; the genetic differentiation increased to 0.01 when data on 23 polymorphic loci were analyzed. The genetic affinity analysis shows the isolated nature of the Parsi and close genetic affinity between the two local populations of Bombay. Although the RFLP technique has several limitations compared with newly defined PCR-based methods, our analysis shows that the RFLP technique is still a useful adjunct method for studying HLA polymorphisms for which only limited data from the populations of the Indian subcontinent are available.

Abstract Asthma is a common and prevalent health problem, globally affecting over 300 million ind... more Abstract Asthma is a common and prevalent health problem, globally affecting over 300 million individuals. Observational and intervention studies have shown beneficial effects of omega-3 [Eicosapentaenoic Acid (EPA) and Docosahexaenoic acid (DHA)] on asthma and exercise-induced bronchoconstriction (EIB). Due to health side effects with pharmacological medication, use of complementary therapies including omega-3 supplementation is gaining impetus. A double-blinded randomised crossover pilot study with 3 weeks of supplementation (3.2 g EPA and 2.2 g DHA or placebo) was conducted to assess the effect of omega-3 supplementation in physically active males with EIB (n = 9, 21 ± 0.9 years, Forced Expiratory Volume in 1-s/Forced Vital Capacity (FEV1/FVC) = 77 ± 1.4). At the start of study, participants showed abnormal lung function, typical drop of >10% in their FEV1 following exercise-challenge tests; elevated levels of Exhaled-breath Nitric oxide, FeNO (>40 ppb). The 3-week supplementation resulted in a significant improvement in post-exercise pulmonary function (PF) (<10% drop in post-exercise FEV1/FVC), supported by significant reduction in serum IL-6 levels (37% reduction). Although no significant changes were observed for Peripheral Blood Mononuclear Cell (PBMC) total lipid composition for EPA/DHA, non-significant increase in total PBMC EPA/DHA with reduction in omega-6 fatty acid (Arachidonic Acid) was observed. This pilot study shows a beneficial effect of 3 weeks of omega-3 supplementation on PF for EIB-participants.

Medicine and Science in Sports and Exercise, Dec 5, 2022

ABSTRACT Introduction South Asians (SAs) have an elevated risk of cardiovascular disease (CVD) co... more ABSTRACT Introduction South Asians (SAs) have an elevated risk of cardiovascular disease (CVD) compared with White Europeans (WEs). Postprandial endothelial function (flow-mediated dilatation (FMD%)) in SA women and SA men with central obesity has not been investigated. Research in other populations has highlighted that a 1% higher FMD% is associated with a ~13% lower risk of future CVD events. We investigated whether FMD% and lipemia, two markers for CVD risk, were higher in SAs versus WEs, whether walking improved FMD% and lipemia, and if there were ethnic differences in the response. Methods Lean premenopausal women (study 1; 12 SA, 12 WE) and men with central obesity (study 2; 15 SA, 15 WE) completed two 2-d trials. On day 1, participants walked for 60 min at 60% of their peak oxygen uptake or rested. On day 2, participants rested and consumed two high-fat meals over 8 h. Repeated ultrasound assessments of endothelial function and venous blood samples for CVD risk markers were taken. Results Compared with WEs, SAs had lower postprandial FMD% (study 1, −1.32%; study 2, −0.54%) and higher postprandial triacylglycerol concentrations (study 1, 0.31 mmol·L−1·h−1; study 2, 0.55 mmol·L−1·h−1). Walking improved postprandial FMD% (study 1, 1.12%; study 2, 0.94%) and resulted in no significant change or small reductions in postprandial triacylglycerol concentrations (study 1, −0.01 mmol·L−1·h−1; study 2, −0.25 mmol·L−1·h−1). Exercise-induced changes in FMD% and triacylglycerol were consistent between ethnic groups. Conclusions Walking mitigated the adverse postprandial effect of a high-fat diet on FMD% to a similar extent in SA and WE women and men, even with no/small improvements in triacylglycerol. This study highlights the importance of exercise to clinically improve FMD% in SAs and WEs.

Molecular Biology Reports, Nov 8, 2013

International Journal of Human Genetics, Dec 1, 2002

The main objectives of this investigation were to establish a database of minisatellite (VNTRs) a... more The main objectives of this investigation were to establish a database of minisatellite (VNTRs) and microsatellite (STRs) allele frequencies for the regionally subdivided populations of the East Midlands, which is suitable for forensic and population genetic investigations. The secondary objective was to determine if Caucasian sub-population heterogeneity exists within the United Kingdom and how this affects the forensic and paternity inferences. Blood samples were collected from random blood donors belonging to five regions of the East Midlands. Using standard molecular genetic techniques, we analysed MS1, MS31,

Indian heart journal, 2004

International Journal of Human Genetics, Mar 1, 2008

Apolipoprotein C3 plays an important role in the receptor mediated hydrolysis of triglyceride ric... more Apolipoprotein C3 plays an important role in the receptor mediated hydrolysis of triglyceride rich lipoproteins (TRLs) by inhibition of lipoprotein lipase (LPL), delayed clearance of which causes hypertriglyceridemia (HTG). Indians are considered to be more vulnerable to the adverse effects of hypertriglyceridemia and consequently its probable sequel of cardiovascular disorders. Several studies have revealed the association of rare allele (S2) of APOC3 (SstI) polymorphism with dyslipidemias and coronary artery diseases. In order to investigate the role and relevance of this polymorphism in Northwest India, the present study aimed to investigate the genetic variation of 3' untranslated region of APOC3 (SstI) in 312 individuals belonging to four endogamous groups (Banias, Brahmins, Jatsikhs and Khatris) of Punjab. Uncommon *S2 allele frequency was 22.6%, 22.5%, 22.7% and 26.2% in Banias, Brahmins, Jatsikhs and Khatris respectively. Higher heterozygosity of 0.39 in Khatris reflected their greater variation at this locus than the other populations. Chi-square analysis did not reveal any significant differences between these populations and other studies from North India (P > 0.05). Comparative analysis of 66 other populations across the world revealed large heterogeneity at this locus whereby, Mongoloid populations have the highest frequencies of *S2 allele (0.19 to 0.48) followed by Indians (0.18 to 0.29), Africans (0.04 to 0.27) and Caucasian populations (0.01 to 0.12). Genetic distance and multivariate analyses showed that Indian population is quite distinct from other Caucasian and Oriental populations. Clinal heterogeneity of predisposing *S2 allele in Asia showed an increasing cline (y = 0.0043x + 0.1209, R 2 = 0.1162) towards North. As this allele is associated with HTG and other cardiovascular complications, differential variation in different populations may have insightful implications for association and medical genetic studies.

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease

Vaccines

Atherosclerosis is the formation of plaque within arteries due to overt assemblage of fats, chole... more Atherosclerosis is the formation of plaque within arteries due to overt assemblage of fats, cholesterol and fibrous material causing a blockage of the free flow of blood leading to ischemia. It is harshly impinging on health statistics worldwide because of being principal cause of high morbidity and mortality for several diseases including rheumatological, heart and brain disorders. Atherosclerosis is perpetuated by pro-inflammatory and exacerbated by pro-coagulatory mediators. Besides several other pathways, the formation of neutrophil extracellular traps (NETs) and the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome contribute significantly to the initiation and propagation of atherosclerotic plaque for its worst outcomes. The present review highlights the contribution of these two disturbing processes in atherosclerosis, inflammation and atherothrombosis in their individual as well as collaborative manner.

The Anthropologist, 2000

AIJSTRACT AIDS a...,-artl'ltSS was in"'stigated in 180 lndivlctu:tlt lhrou&h tdcphonleconversario... more AIJSTRACT AIDS a...,-artl'ltSS was in"'stigated in 180 lndivlctu:tlt lhrou&h tdcphonleconversarion in 32 villages in (OtJr dirtuloos (from 0-40 kms) of Ludhiana city of Punjab. Oear c~t decreasina trend or A I OS con;c:iousneiiS away from the cily in aU the four direc:tiQn5 waJ evident i.e. to~~>'lrds. Nonh (y.a .(),J7<:lx + 14.S9. r • 0.9$96), South (y # .(),4Q)x + 14.28, r • 0.9610), l;a$l (y • .0.4187x + 15.14, r • 0.9671) and Wett (y • •0.4037x • 14.71, r • 0.%75). Vari:.tions in misconceptJuns art trinif'l& (.S•I .S%) in 0•20 kms tan,£e but quite high (35-60%) in l$.40 kms ~It howt,•t r. lhtst Wtte fotmd to be insignificanl at 5% level (;('!= 1 .65.d.f=4~ (X!= I A.d.f=l)rupcctively. We hl\'e used the multiple rep-eS.$torl (d l$uncc \'$11Wlltcnen) to gen• er.111.: the hypothesis that d is~aru dwt"lkrs '""'*Y (tom the d11es ~c uM,.,'lrt: about AJOS hullabaJoo.

Inflammation, oxidative stress, apoptosis and neovascularization are risky parameters which influ... more Inflammation, oxidative stress, apoptosis and neovascularization are risky parameters which influence different phases in the pathogenesis of age related macular degeneration (AMD). Beside other mediators, this multitiered and complex event of retinal worsening has been exposed to be orchestrated by small non coding RNA fragments that bind to specific mRNAs and modulate their post transcriptional regulation and gene expression in retina. Several microRNAs (miRNAs) have been revealed which are expressed in retina and influence its functionality. These miRNA fragments play significant role in the development and maintenance of photoreceptors hence, dysregulation of them may augment severe retinal etiopathology. This comprehensive review summarizes the role and relevance of several known miRNAs along with their potential utilities as therapeutic targets in AMD pathogenesis.

International Journal of Environmental Research and Public Health

Background: Globally, type 2 diabetes mellitus (T2DM) is one of the fastest-growing noncommunicab... more Background: Globally, type 2 diabetes mellitus (T2DM) is one of the fastest-growing noncommunicable multifactorial and polygenic diseases, which leads to many health complications and significant morbidity and mortality. South Asians have a high genetic predisposition to T2DM, with India being home to one in six diabetics. This study investigates the association of selected genetic polymorphisms with T2DM risk and develops a polygenic risk score (PRS). Methods: A case–control study recruited fully consented participants from a population of Jat Sikhs in north India. DNA samples were genotyped for a range of polymorphisms and odds ratios were calculated under several genetic association models. Receiver operating characteristic (ROC) curves were produced for combinations of the PRS and clinical parameters. Results: The GSTT1(rs17856199), GSTM1(rs366631), GSTP1(rs1695), KCNQ1(rs2237892), ACE(rs4646994), and TCF7L2(rs12255372; rs7903146; rs7901695) polymorphisms were associated with in...

Genes

Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation ca... more Physical inactivity and a poor diet increase systemic inflammation, while chronic inflammation can be reduced through exercise and nutritional interventions. The mechanisms underlying the impacts of lifestyle interventions on inflammation remain to be fully explained; however, epigenetic modifications may be critical. The purpose of our study was to investigate the impacts of eccentric resistance exercise and fatty acid supplementation on DNA methylation and mRNA expression of TNF and IL6 in skeletal muscle and leukocytes. Eight non-resistance exercise-trained males completed three bouts of isokinetic eccentric contractions of the knee extensors. The first bout occurred at baseline, the second occurred following a three-week supplementation of either omega-3 polyunsaturated fatty acid or extra virgin olive oil and the final bout occurred after eight-weeks of eccentric resistance training and supplementation. Acute exercise decreased skeletal muscle TNF DNA methylation by 5% (p = 0.0...

Journal of Bodywork and Movement Therapies, 2022