South Asian Population Research Articles

Analysis of the frequency distribution of five single-nucleotide polymorphisms of the MTRRgene in a Chinese pediatric population with acute lymphoblastic leukemia.

The objective of the present study was to examine the frequency distribution of five single-nucleotide polymorphisms (SNPs; rs1801394 A>G, rs1532268 C>T, rs162036 A>G, rs10380 C>T, and rs9332 C>T) of the methionine synthase reductase (MTRR) gene, their effects on methotrexate (MTX) concentration, and the risk of relapse in a Chinese pediatric population with acute lymphoblastic leukemia (ALL). This was a retrospective single-center study, and all analyses were exploratory. Pediatric Department of Beijing Shijitan Hospital, Capital Medical University, Beijing, China. One hundred and forty pediatric patients with ALL. All patients were treated according to the Chinese Children's Leukemia Group (CCLG)-ALL 2008 protocol. Serum MTX concentrations were measured using fluorescence polarization immunoassay. Genotyping of five SNPs was performed using the Sequenom MassARRAY iPLEX platform. Chinese children with ALL had a significantly lower frequency of rs1801394 G than European (EUR) and South Asian (SAS) populations; significantly lower frequency of rs1532268 T than American (AMR), EUR, and SAS populations; and significantly lower frequencies of rs162036 G, rs10380 T, and rs9332 T than African and AMR populations (p<0.01). Seven haplotypes were observed, with the ACACC being the most common haplotype (49.9%) in our study. The median dose-normalized concentrations of MTX in serum at 24h in children with rs1532268 CT and TT genotypes were significantly higher than those with CC genotype (p=0.04). Compared with children with AA-CC-AA-CC-CC diplotype, a significantly higher risk of relapse was observed in children with AG-CC-AA-CC-CC and AG-CC-AG-CC-CC diplotypes (p=0.03 and 0.003, respectively). The present study confirmed the ethnic differences in the distribution of MTRR rs1801394, rs1532268, rs162036, rs10380, and rs9332 polymorphisms. The rs1532268 polymorphism had greater effects on MTX disposition. The AG-CC-AA-CC-CC and AG-CC-AG-CC-CC diplotypes were significantly associated with higher risk of relapse of ALL.

Comparing the acceptability of total diet replacement and food-based low energy diets for type 2 diabetes remission amongst South Asians: a public and patient involvement activity

Background: With type 2 diabetes prevalence rising, low energy diets (total diet replacement and food-based low energy diets) are increasingly used to induce weight loss and achieve diabetes remission. The effectiveness of these diets has been primarily tested in the UK white population but not in the south Asian population at high risk of diabetes. Obtaining the opinion of members of the community on what would constitute a culturally acceptable diet is essential for successful interventions aiming to achieve diabetes remission in south Asians. Methods: We organised two patient and public involvement activities in the North West of England to understand views of people from the south Asian population on whether low energy diets (850 Kcal) in the form of total diet replacement or food-based meals, are acceptable dietary interventions to achieve type 2 diabetes remission. Results: Thirteen people, with either type 2 diabetes or having someone with diabetes in the family attended a virtual or a face-to-face meeting. Low energy total diet replacement in the form of soups and shakes was considered unacceptable, while there was a preference for a culturally tailored low energy food-based diet. Ready-made portion controlled catered meals were suggested as a likely approach to improve adherence. Conclusions: This work provided valuable insights to shape a future study looking at the feasibility of a catered meal low-energy dietary intervention to induce T2D remission in primary care within the south Asian population.

A microRNA binding site polymorphism in the 3\u2032 UTR region of VEGF-A gene modifies colorectal cancer risk based on ethnicity: a meta-analysis

BackgroundVascular endothelial growth factor A (VEGF-A) plays an integral role in angiogenesis by contributing to growth, development, and metastasis of solid tumors. Recently, a single-nucleotide polymorphism +936C/T located in the VEGF-A 3′ untranslated region (UTR) facilitated the susceptibility of colorectal cancer. The association between VEGF-A gene polymorphism +936C/T and colorectal cancer risk has been widely studied in the last decade, but presently, the results furnished remain enigmatic. Hence, the study aimed to investigate the association between VEGF-A +936C/T miRNA binding site polymorphism and the risk of developing colorectal cancer.MethodsThis meta-analysis included 13 published case-control studies covering 3465 cases (colorectal cancer) and 3476 healthy controls. Publication bias was examined by means of Begg’s funnel plots and Egger’s regression tests. The quality of the studies included was evaluated using Newcastle-Ottawa scale. Subgroup analyses were performed in accordance to the various ethnicities of the study subjects and the study quality.ResultsFrom the data obtained, it is implied that VEGF-A +936C/T polymorphism did not correlate with elevated colorectal cancer risk in all genetic models. But the results acquired from the subgroup analysis in over dominant model (CT vs. CC + TT: OR = 1.5047, 95% CI = 1.19–1.90) suggest that VEGF-A +936C/T polymorphism leads to the raise in the risk of developing CRC among the East Asian population. No association was observed in Caucasian and South Asian population.ConclusionsOur results indicate that VEGF-A +936C/T polymorphism is not a risk factor for developing CRC in Caucasian and South Asian population. However, the East Asian population was related to an increased risk of developing colorectal cancer due to the presence of the minor allele.

P184 Are there any ethnic differences in the response to Janus Kinase Inhibitor therapy for the treatment of rheumatoid arthritis?

Abstract Background/Aims Baricitinib is an oral, synthetic Janus Kinase inhibitor. It has become a commonly used drug in the treatment of rheumatoid arthritis (RA), both as combination therapy and monotherapy. Previous studies have compared drug efficacy in different ethnicities, but no studies have compared the efficacy of baricitinib for the treatment of RA in different ethnicities. Given the large South Asian population in Leicestershire, we reviewed our cohort of RA patients on baricitinib to see whether there is any difference in drug response rates between the Asian and Caucasian cohorts. Methods This was a retrospective study. Patients included were those under the care of rheumatology at University Hospitals of Leicester (UHL) with a diagnosis of RA and either receiving baricitinib, or had received it in the past. Data was collected using the UHL IT systems, clinic letters, and pharmacy records. In addition to ethnicity, we reviewed patient age, gender, concurrent DMARDs used, previous biologics used, baseline and post-treatment DAS28, dropout from therapy, baseline biochemical assays (anti-CCP and RF status) and radiographic findings. Independent T-test was used to compare continuous data and the Pearson Chi-Square test was used to compare categorical data. SPSS was used to analyse the results. Results 120 patients were included in the analysis and data was analysed with PFA. There was no statistically significant difference in the mean DAS28 at baseline (Asian 5.17 vs Caucasian 4.65, p value 0.107) and post-treatment (Asian 2.83 vs Caucasian 3.33, p value 0.404) (see table 1). Comparing both ethnicities, there was no statistically significant difference in previous biologics used, the presence or absence of anti-CCP and RF, and radiographic findings of erosions. Limitations of the study include the low proportion of post treatment DAS28 values recorded and absence of data comparing primary or secondary biologic failure. Conclusion This is the first study of its kind and found no significant difference in baricitinib response between the Asian and Caucasian cohorts. Future studies are needed to evaluate this subject further. Such data is important as it can contribute to a body of evidence that may in future help inform clinical decision making. Disclosure A. Jubber: None. W.H.Z. Hussain: None. A. Moorthy: None.

A stable isotope perspective on archaeological agricultural variability and Neolithic experimentation in India

Agriculture has been crucial in sustaining human populations in South Asia across dramatically variable environments for millennia. Until recently, however, the origins of this mode of subsistence in India have been discussed in terms of population migration and crop introduction, with limited focus on how agricultural packages were formulated and utilised in local contexts. Here, we report the first measurements of stable carbon and nitrogen isotope values in well-preserved charred crop remains from sites spanning the Neolithic/Chalcolithic to the Early Historic in two very different environmental zones: tropical East India and the semi-arid Deccan. The results show that this approach offers direct insight into prehistoric crop management under contrasting environmental constraints. Our preliminary results plausibly suggest that early farmers in India experimented with and made strategic use of water and manure resources in accordance with specific crop requirements and under varying environmental constraints. We suggest that the development of modern crop isotope baselines across India, and the application of this methodology to archaeological assemblages, has the potential to yield detailed insight into agroecology in India's past.

Identification of genetic effects underlying type 2 diabetes in South Asian and European populations

South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10−8 to 5.2 × 10−12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations.

Mining of molecular insights of CYP2A6 and its variants complex with coumarin (CYP2A6*-coumarin) using molecular dynamics simulation

CYP2A6 is a very important enzyme that plays a crucial role in nicotine compounds and is responsible for the metabolism of more than 3% drugs of total metabolized drugs by the CYP family and reported as one of very important pharmacogenes. CYP2A6 is highly polymorphic in nature and reported with more than 40 variants, most of these variants are SNPs originated and population specific. It has been well observed and reported that the presence of these population-specific non-synonymous SNPs in CYP2A6 alters the rate of drug metabolism and as a functional consequence, drugs produce an abnormal response. Though genomics and pharmacogenomics studies are there, very less is known about the structural effects of these SNPs on molecular-interaction and folding of CYP2A6. To fill the knowledge gap, SNPs based four variants, i.e., CYP2A6*2, CYP2A6*18, CYP2A6*21, and CYP2A6*35, which are frequently reported in the South Asian population, were considered for the study. Coumarin (DB04665), a well reported drug, is considered as a model substance, and the effect of all four variants on ‘CYP2A6*-coumarin’ complex was studied. MD simulation-based analysis (at 200 ns) was performed and comparative analysis with respect to wild type ‘CYP2A6-coumarin’ complex was done. Though observation didn’t find any global effect on complete complex but found some crucial minor-local alteration in interaction and folding process. It is assumed that the change due to SNPs in the single amino acid did not bring global change in physiochemical properties of CYP2A6* but caused local-trivial changes which are very crucial for its metabolic activity. Communicated by Ramaswamy H. Sarma

IDF21-0131 What Is Driving Diabetes and Diabetes Complications in British Columbia (BC), Canada?

Background: British Columbia (BC) is a Western Canadian province with 5.02 million people, ethnic diversity (Aboriginal, Chinese, South Asian) & >70% rural/remote/isolated geography. For 40 years, intermittent efforts in BC & Canada to improve chronic disease & diabetes management had little positive effect. Ideally, healthcare services & planning should be driven by strong data & evidence. No integrated system exists in BC to track, study, understand, manage & improve diabetes care. No comprehensive BC diabetes environmental scan has ever been conducted before. Aim: The BC Provincial Diabetes Evaluation is a quality improvement project to identify & better understand major gaps/barriers; & practical solutions for data-driven diabetes care management redesign in BC; so that all 470,000 diabetes people receive improved, timely, appropriate, cost-effective care that is locally/culturally/ethnically-sensitive, no matter where they live in BC. Method:1.Retrospective, open quantitative multi-source data analysis2.Prospective, open qualitative data analysis3.Knowledge Translation phase including Diabetes Heat Maps with diabetes performance measures; co-morbidities (*CKD, CAD, CHF); major procedures/surgeries (*renal dialysis, cardiac PCI, lower limb amputation) Results: BC’s geographical, socio-economic & lifestyle factors are drivers of diabetes & complications (by each of BC geographical health authority): • Fraser Health Authority (FHA): with BC’s highest population density, diabetes incidence & prevalence driven by BC's 2nd highest immigrant, non-English-speaking (ESL); highest South Asian population; & unhealthy lifestyle (diet, obesity, physical inactivity)#; associated with BC’s 2nd highest diabetes complications*, hospitalization cost & premature mortality; with an overall younger FHA population. • Northern Health Authority (NHA): with BC’s 2nd highest diabetes incidence & prevalence driven by highest rurality (64% of BC’s land mass), Aboriginal, low-education population; lifestyle# & smoking; associated with BC’s 2nd highest diabetes complications* & highest premature mortality; with an overall younger NHA population. • Vancouver Coastal Health Authority (VCHA): with BC’s highest immigrant, ESL, Chinese, low-income population; 2nd highest South Asian & BC population density; offset by a younger, healthier VCH population; associated with mid-range diabetes incidence & prevalence; & BC’s highest hospitalization cost. • Vancouver Island Health Authority (VIHA): BC’s highest elderly population; mid-range rurality, Aboriginal, immigrant, low-income population; associated with 2nd lowest incidence & prevalence; & BC’s lowest hospitalization cost. • Interior Health Authority (IHA): with BC’s 2nd highest elderly, Aboriginal, low-education population living alone; 2nd highest rurality; lowest ESL population; associated with BC’s lowest diabetes incidence & prevalence. Discussion: Substantial variation exists between BC's 5 geographical health authorities for diabetes outcomes, health determinants & cost. The current state of diabetes as an ambulatory-care-sensitive-condition indicates an inadequate primary healthcare system throughout BC & Canada. Barriers to accessing diabetes resources contributed to 80% of diabetes care provided by GPs in BC & Canada. BC has a higher reliance on physicians & lower usage of allied healthcare providers for diabetes care than other provinces. Without coordinated BC provincial diabetes care planning or services, a fragmented, non-standardized, patchwork system has resulted with negative health outcomes & high impact on BC's entire healthcare system (similar across Canada). Our BC Provincial Diabetes Evaluation Knowledge Translation findings will help with diabetes care management redesign; & improve the trajectory of diabetes, outcomes & healthcare utilization in BC.

Clinical Profile of Anti-Transcription Intermediary Factor-1 Gamma-Positive Adults from a Single Tertiary Care Center

Anti-transcription intermediary factor-1 γ (TIF-1 γ) antibody is a myositis-specific antibody. These cases had specific clinical features in the past studies. There is no published data on such patients from South Asia. We retrospectively looked at data from patients with positive anti-TIF-1 γ antibodies from our hospital database between May 2019 and October 2020. Their clinical presentation, muscle and extra muscular involvement, investigations, presence of malignancy, and treatment with subsequent follow-up were retrieved using the electronic medical records. TIF-1 γ was rare at our center and was 2.46% out of the total positive myositis immunoblot results. Seven adult patients had significant anti-TIF-1 γ positivity. Five out of them had clinical muscle weakness; none had severe or respiratory muscle weakness. No patients had cancer-associated myositis. The skin was the most common extra muscular organ involved. The absence of cancer-associated myositis with anti-TIF-1 γ subjects in our series may represent the difference in phenotype in the South Asian population.

EHealth Literacy in a Sample of South Asian Adults in Edmonton, Alberta, Canada: Subanalysis of a 2014 Community-Based Survey.

BackgroundDigital health interventions are efficient and flexible methods for enhancing the prevention and management of cardiovascular disease and type 2 diabetes. However, little is known about the characteristics associated with eHealth literacy in the Canadian South Asian population.ObjectiveThe aim of this study is to describe perceived eHealth literacy and explore the extent to which it is associated with sociodemographic, health status, and technology use variables in a subset of South Asian Canadians.MethodsWe analyzed data from the e-Patient Project survey, a mixed-mode cross-sectional survey that occurred in 2014. The eHealth Literacy Scale (eHEALS) was used to measure eHealth literacy in a convenience sample of 511 English- or Punjabi-speaking South Asian adults recruited from a community pharmacy, a family physician office, and community events in Edmonton, Alberta. Multivariable quantile regression was used to explore variables associated with eHealth literacy.ResultsThe analysis was restricted to 301 internet users (mean age 39.9, SD 14.8 years; 166/301, 55.1% female) who provided responses to all 8 eHEALS questions and complete demographic information. The mean overall eHEALS score was 29.3 (SD 6.8) out of 40, and 71.4% (215/301) agreed to at least 5 out of the 8 eHEALS items. The eHEALS item with the lowest level of agreement was “I can tell high-quality health resources from low-quality health resources on the internet” (182/301, 60.5%). Although there were statistically significant differences in eHEALS scores according to age, educational achievement, language preference, and the presence of chronic medical conditions, multivariable regression analysis indicated that language preference was the only variable independently associated with eHealth literacy (coefficient –6.0, 95% CI –9.61 to –2.39).ConclusionsIn our sample of South Asian Canadian internet users, preference for written health information in languages other than English was associated with lower eHealth literacy. Opportunities exist to improve eHealth literacy using culturally and linguistically tailored interventions.

Cross-ethnic analysis of common gene variants in hemostasis show lopsided representation of global populations in genetic databases

A majority of studies reporting human genetic variants were performed in populations of European ancestry whereas other global populations, and particularly many ethnolinguistic groups in other continents, are heavily underrepresented in these studies. To investigate the extent of this disproportionate representation of global populations concerning variants of significance to thrombosis and hemostasis, 845 single nucleotide polymorphisms (SNPs) in and around 34 genes associated with thrombosis and hemostasis and included in the commercial Axiom Precision Medicine Research Array (PMRA) were evaluated, using gene frequencies in 3 African (Somali and Luhya in East Africa, and Yoruba in West Africa) and 14 non-African (admixed American, East Asian, European, South Asian, and sub-groups) populations. Among the populations studied, Europeans were observed to be the best represented population by the hemostatic SNPs included in the PMRA. The European population also presented the largest number of common pharmacogenetic and pathogenic hemostatic variants reported in the ClinVar database. The number of such variants decreased the farther the genetic distance a population was from Europeans, with Yoruba and East Asians presenting the least number of clinically significant hemostatic SNPs in ClinVar while also being the two genetically most distinct populations from Europeans among the populations compared. Current study shows the lopsided representation of global populations as regards to hemostatic genetic variants listed in different commercial SNP arrays, such as the PMRA, and reported in genetic databases while also underlining the importance of inclusion of non-European ethnolinguistic populations in genomics studies designed to discover variants of significance to bleeding and thrombotic disorders.

“Tension” and distress in South Asia: A systematic literature review

This systematic literature review summarizes academic knowledge on “tension” among South Asian and diaspora populations. “Tension” (sometimes transliterated as tenshun) is a term used across South Asia to talk about stress and distress, but the existing literature is dispersed and has never been analyzed synthetically. Following PRISMA guidelines, we searched 8 academic databases and solicited additional contributions from professional listservs. This process led to a final group of 122 records addressing “tension” in South Asian groups. The majority of studies took place in India and focused on mixed-gender adult samples. Many records reported differences in “tension” experience and vulnerability based on gender, while a few addressed differences based on age or socioeconomic group. Across records, “tension” described a wide range of physical and affective symptoms, and reflected distress experiences ranging from everyday hassles up to severe distress or even suicidality. “Tension” was often conceptualized via a hydraulic ethnopsychological model in which pent-up emotion expressed itself through physical or affective symptoms. Tension was often understood as an intermediary state between external stressors and internal states of pathology. People endorsed a variety of internal and external coping strategies, but several emphasized that only meaningful changes in adverse circumstances could solve “tension.” There was no consensus on whether “tension” is best characterized as an idiom of distress or a cultural syndrome, but based on the breadth of results reflected in this literature, we suggest that it is best understood under the umbrella term cultural concept of generalized psychosocial distress. To address gaps in the literature on “tension,” future research could work among populations outside India, could conduct direct comparative studies of how experiences vary by caste, gender, age, and socioeconomic status, and could explore the potential clinical value of “tension” for broaching discussions between patients and providers about distress.

Physical Activity Experiences of South Asian Migrant Women in Western Australia: Implications for Intervention Development.

The benefits of physical activity are widely recognised; however, physical activity uptake remains low in South Asian populations. South Asian migrant women face health risks as they adapt to new cultures, and these risks are often intensified through their limited participation in physical activity as one of the behaviours that promote positive health outcomes. Three focus group discussions with sixteen South Asian migrant women aged between 33 and 64 years, with a median age of 48 years and who live in Western Australia, were conducted. Thematic analysis of the transcribed qualitative data was completed to explore and uncover South Asian women’s experiences with physical activity, as well as their motivation, beliefs, attitudes, and knowledge about physical activity. Five major themes emerged after coding and analysing the data. The themes included the women’s knowledge of physical activity, their general attitudes and beliefs surrounding physical activity, the advantages and disadvantages of participation in physical activity, their experiences with physical activity, and the barriers, challenges, and facilitators surrounding physical activity. Recommendations are proposed to increase physical activity among this group to improve overall health and wellbeing and implications for intervention development are discussed.

Understanding signatures of positive natural selection in human zinc transporter genes

Zinc is an essential micronutrient with a tightly regulated systemic and cellular homeostasis. In humans, some zinc transporter genes (ZTGs) have been previously reported as candidates for strong geographically restricted selective sweeps. However, since zinc homeostasis is maintained by the joint action of 24 ZTGs, other more subtle modes of selection could have also facilitated human adaptation to zinc availability. Here, we studied whether the complete set of ZTGs are enriched for signals of positive selection in worldwide populations and population groups from South Asia. ZTGs showed higher levels of genetic differentiation between African and non-African populations than would be randomly expected, as well as other signals of polygenic selection outside Africa. Moreover, in several South Asian population groups, ZTGs were significantly enriched for SNPs with unusually extended haplotypes and displayed SNP genotype-environmental correlations when considering zinc deficiency levels in soil in that geographical area. Our study replicated some well-characterized targets for positive selection in East Asia and sub-Saharan Africa, and proposes new candidates for follow-up in South Asia (SLC39A5) and Africa (SLC39A7). Finally, we identified candidate variants for adaptation in ZTGs that could contribute to different disease susceptibilities and zinc-related human health traits.

Constructing a South Asian cardiovascular disease: a qualitative analysis on how researchers study cardiovascular disease in South Asians

BackgroundDebates on the use of race in biomedical research have typically overlooked immigrant groups outside of the black-white racial dichotomy. Recent biomedical research on South Asians and cardiovascular disease provides...

Anthropogenic climate change drives melting of glaciers in the Himalaya.

The Himalayan glaciers provide water to a large population in south Asia for a variety of purposes and ecosystem services. As a result, regional monitoring of glacier melting and identification of the drivers are important for understanding and predicting future cryospheric melting trends. Using multi-date satellite images from 2000 to 2020, we investigated the shrinkage, snout retreat, thickness changes, mass loss and velocity changes of 77 glaciers in the Drass basin, western Himalaya, India. During this period, the total glacier cover has shrunk by 5.31 ± 0.33 km2. The snout retreat ranged from 30 to 430m (mean 155 ± 9.58m). Debris cover had a significant impact on glacier melting, with clean glaciers losing ~ 5% more than debris-covered glaciers (~ 2%). The average thickness change and mass loss of glacier have been - 1.27 ± 0.37 and - 1.08 ± 0.31m w.e.a-1, respectively. Because of the continuous melting and the consequent mass loss, average glacier velocity has reduced from 21.35 ± 3.3m a-1 in 2000 to 16.68 ± 1.9m a-1 by 2020. During the observation period, the concentration of greenhouse gases (GHGs), black carbon (BC) and other pollutants from vehicular traffic near the glaciers increased significantly. Increasing temperatures, caused by a significant increase in GHGs, black carbon and other pollutants in the atmosphere, are driving glacier melting in the study area. If the current trend continues in the future, the Himalayan glaciers may disappear entirely, having a significant impact on regional water supplies, hydrological processes, ecosystem services and transboundary water sharing.

Excessive replacement changes drive evolution of global sheep prion protein (PRNP) sequences.

Sheep prion protein (PRNP) is the major host genetic factor responsible for susceptibility to scrapie. We aimed to understand the evolutionary history of sheep PRNP, and primarily focused on breeds from Turkey and Ethiopia, representing genome-wise ancient sheep populations. Population molecular genetic analyses are extended to European, South Asian, and East Asian populations, and for the first time to scrapie associated haplotypes. 1178 PRNP coding region nucleotide sequences were analyzed. High levels of nucleotide diversity driven by extensive low-frequency replacement changes are observed in all populations. Interspecific analyses were conducted using mouflon and domestic goat as outgroup species. Despite an abundance of silent and replacement changes, lack of silent or replacement fixations was observed. All scrapie-associated haplotype analyses from all populations also showed extensive low-frequency replacement changes. Neutrality tests did not indicate positive (directional), balancing or strong negative selection or population contraction for any of the haplotypes in any population. A simple negative selection history driven by prion disease susceptibility is not supported by the population and haplotype based analyses. Molecular function, biological process enrichment, and protein-protein interaction analyses suggested functioning of PRNP protein in multiple pathways, and possible other functional constraint selections. In conclusion, a complex selection history favoring excessive replacement changes together with weak purifying selection possibly driven by frequency-dependent selection is driving PRNP sequence evolution. Our results is not unique only to the Turkish and Ethiopian samples, but can be generalized to global sheep populations.

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Performance of Serum β2-Microglobulin– and β-Trace Protein–Based Panel Markers and 2021 Creatinine- and Cystatin-Based GFR Estimating Equations in Pakistan

Genetic structure and phylogeography of Echinococcus granulosus sensu stricto genotypes G1 and G3 in Pakistan and other regions of the world based on nad5 gene.

Pakistan is a neglected endemic focus for Echinococcus granulosus sensu lato, a zoonotic parasite species complex with the ability to infect wide spectrum of hosts. Wide gaps exist in literature for etiological agents of cystic echinococcosis (CE) in Pakistan due to a very low number of studies on identifying the exact genotypes involved in epidemiological manifestation of this disease. Focusing on transmission patterns and epidemiological dynamics, this study aimed at investigating infective genotypes among the cattle population of south Punjab, Pakistan, employing a mitochondrial marker nad5 (680bp). Nucleotide sequences retrieved from 28 hydatid cyst isolates displayed considerable intraspecific variation revealing the existence of G3 and G1 strains of Echinococcus granulosus sensu stricto. The G3 genotype emerged as the predominant cause (78.57%) of hydatidosis in cattle. Apart from this, to understand phylogeographical relations, homologous nucleotide sequences of the partial nad5 gene from six major regions of the world were employed in the population genetics analysis to have an insight into genetic variability and demographics of G3 genotype in particular. Diversification of G3 and its haplotypes in Pakistan (n=11) and other regions of the world (India, Iran, Turkey, Italy and France) was demonstrated. It was further demonstrated that the South Asian population (Pakistan and India) was highly differentiated from the other regions. It could, therefore, be speculated that G3 is diverging and expanding its population with South Asia as the main focal point.

Replacing dietary carbohydrates and refined grains with different alternatives and risk of cardiovascular diseases in a multi-ethnic Asian population

Cardiovascular diseases (CVDs) are a major cause of deaths worldwide, but prospective data on dietary risk factors for CVD in South and Southeast Asian populations are sparse. We aimed to evaluate the relation between macronutrient and food intakes and incidence of major adverse cardiovascular events (MACEs) in a multi-ethnic Asian population. We used data from the Singapore Multi-Ethnic Cohort (n=12,408), a prospective cohort of ethnic Chinese, Malay, and Indian adults aged 21‒65 y recruited between 2004 and 2010. Dietary intakes were assessed using a validated food-frequency questionnaire, and the incidence of MACEs was ascertained through data linkage with national registries. A Cox proportional hazards model was used to evaluate the associations between dietary intakes and MACE risk. Over a mean (SD) follow-up of 10.1 (2.3) y, 746 incident cases of MACEs were documented. We observed a direct association between carbohydrate intake and MACE risk (highest vs. lowest quartile, HR: 1.35; 95% CI: 1.07, 1.71; P-trend = 0.001). Replacing 5% of energy from carbohydrate with polyunsaturated fat (HR: 0.79; 95% CI: 0.69, 0.91) but not saturated fat (HR: 0.95; 95% CI: 0.84, 1.09) was significantly associated with a lower MACE risk. In terms of food groups, replacing 1 serving/d of refined grains with fruit (HR: 0.93; 95% CI: 0.87, 0.99), vegetables (HR: 0.92; 95% CI: 0.85, 1.00), and dairy (HR: 0.90; 95% CI: 0.82, 0.98) was associated with lower MACE risk. Cholesterol intake was associated with a higher MACE risk in ethnic Indians (highest vs. lowest quartile, HR: 2.40; 95% CI: 1.53, 3.75; P-trend<0.001) but not in ethnic Malay or Chinese (P-interaction = 0.015). Moderating carbohydrate intakes by increasing polyunsaturated fat intake and replacing refined grains with fruits, vegetables, and dairy was associated with lower MACE risk in Asian populations.