Lack of Association of Bone Morphogenetic Protein 2 Gene Haplotypes with Bone Mineral Density, Bone Loss, or Risk of Fractures in Men

Introduction. The association of bone morphogenetic protein 2 (BMP2) with BMD and risk of fracture was suggested by a recent linkage study, but subsequent studies have been contradictory. We report the results of a study of the relationship between BMP2 genotypes and BMD, annual change in BMD, and risk of fracture in male subjects. Materials and Methods. We tested three single-nucleotide polymorphisms (SNPs) across the BMP2 gene, including Ser37Ala SNP, in 342 Caucasian Englishmen, comprising 224 control and 118 osteoporotic subjects. Results. BMP2 SNP1 (Ser37Ala) genotypes were found to have similar low frequency in control subjects and men with osteoporosis. The major informative polymorphism, BMP2 SNP3 (Arg190Ser), showed no statistically significant association with weight, height, BMD, change in BMD at hip or lumbar spine, and risk of fracture. Conclusion. There were no genotypic or haplotypic effects of the BMP2 candidate gene on BMD, change in BMD, or fracture risk identified in this cohort

Paraoxonase 1 GENE polymorphisms contribute to coronary artery disease risk

Polymorphisms in paraoxonase 1 (PON1) coding for PON1 enzyme have been studied as genetic markers of coronary artery disease (CAD). PON1 Q192R and PON1 L55M polymorphisms have been analyzed extensively, but data on association and role of these polymorphisms in the etiology of CAD are conflicting. In this study, we tested the genetic association between PON1 Q192R and PON1 L55M polymorphisms and CAD among north Indians. MATERIALS AND METHODS: Two hundred eighty-five angiographically proven patients with coronary artery disease and 200 sex-matched and ethnically matched controls were genotyped for 2 PON1 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Genotype/ allele frequencies were compared in patients and controls using the chi-square test. RESULTS: At PON1-192 locus, there were significant differences between patients and controls (P< 0.05), leading to significant odds ratios for RR genotype (OR= 1.92, CI: 1.19-3.10) and *R allele (OR= 1.30, CI: 1.00-1.70). These odds ratios were higher in the sub-sample of smokers (2.84 and 1.45, respectively). Binary logistic regression analysis also confirmed that *R allele carriers (QR and RR) have a higher risk of CAD (OR= 3.54, CI: 1.67-5.53). PON1-55 locus did not show significant differences between patients and controls, but LL genotype and *L allele were significant risk factors in the nonsmoker group. RL haplotype was also significantly associated with CAD risk (OR= 1.44, CI: 1.08-1.93). CONCLUSIONS: PON1-192R allele and RR genotype are significantly associated with CAD patients from the north Indian population (Uttar Pradesh). This association was stronger in smokers, supporting the conclusion that an interaction between PON1 activity and smoking augments CAD risk. Further studies with larger sample size are warranted to confirm these associations in different Indian populations

Most of the extant mtDNA boundaries in South and Southwest Asia were likely shaped during the initial settlement of Eurasia by anatomically modern humans

BACKGROUND:Recent advances in the understanding of the maternal and paternal heritage of south and southwest Asian populations have highlighted their role in the colonization of Eurasia by anatomically modern humans. Further understanding requires a deeper insight into the topology of the branches of the Indian mtDNA phylogenetic tree, which should be contextualized within the phylogeography of the neighboring regional mtDNA variation. Accordingly, we have analyzed mtDNA control and coding region variation in 796 Indian (including both tribal and caste populations from different parts of India) and 436 Iranian mtDNAs. The results were integrated and analyzed together with published data from South, Southeast Asia and West Eurasia.RESULTS:Four new Indian-specific haplogroup M sub-clades were defined. These, in combination with two previously described haplogroups, encompass approximately one third of the haplogroup M mtDNAs in India. Their phylogeography and spread among different linguistic phyla and social strata was investigated in detail. Furthermore, the analysis of the Iranian mtDNA pool revealed patterns of limited reciprocal gene flow between Iran and the Indian sub-continent and allowed the identification of different assemblies of shared mtDNA sub-clades.CONCLUSIONS:Since the initial peopling of South and West Asia by anatomically modern humans, when this region may well have provided the initial settlers who colonized much of the rest of Eurasia, the gene flow in and out of India of the maternally transmitted mtDNA has been surprisingly limited. Specifically, our analysis of the mtDNA haplogroups, which are shared between Indian and Iranian populations and exhibit coalescence ages corresponding to around the early Upper Paleolithic, indicates that they are present in India largely as Indian-specific sub-lineages. In contrast, other ancient Indian-specific variants of M and R are very rare outside the sub-continent.This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at [email protected]

Unity in diversity: an overview of the genomic anthropology of India

This is an Accepted Manuscript of an article published by Taylor & Francis in Annals of Human Biology on 16th Jun 2014, available online: http://dx.doi.org/10.3109/03014460.2014.922615Context: India is considered a treasure for geneticists and evolutionary biologists due to its vast human diversity, consisting of more than 4500 anthropologically well-defined populations (castes, tribes and religious groups). Each population differs in terms of endogamy, language, culture, physical features, geographic and climatic position and genetic architecture. These factors contributed to India-specific genetic variations which may be responsible for various common diseases in India and its migratory populations. As a result, interpretations of the origins and affinities of Indian populations as well as health and disease conditions require complex and sophisticated genetic analysis. Evidence of ancient human dispersals and settlements is preserved in the genome of Indian inhabitants and this has been extensively analysed in conventional and genomic analyses. Objective and methods: Using genomic analyses of STRs and Alu on a set of populations, this study estimates the level and extent of genetic variation and its implications. Results: The results show that Indian populations have a higher level of unique genetic diversity which is structured by many social processes and geographical attributes of the country. Conclusion: This overview highlights the need to study the anthropological structure and evolutionary history of Indian populations while designing genomic and epigenomic investigations. © 2014 Informa UK Ltd

A study of morpho-behavioural and genetic traits among Dhimars of Mandla, Madhya Pradesh, India

Summary. — 75 adult males of Dhimar community of Mandla district of Madhya Pradesh (India) were studied for the P.T.C., Colour Vision Defect, Handedness, Tounge Gymnastics, and Mid Phalangeal Hair. Dhimars is an endogamous fishermen and palanquin bearing community and this study aims to investigate polymorphisms of somes genetic and morpho-behavioural traits among Dhimars and evaluate their affinities with other populations.ÉTUDE DE CARACTÈRES MORPHOLOGIQUES ET GÉNÉTIQUES CHEZ LES DHIMARS DE MANDLA, MADHYA PRADESH, INDE. Résumé. — Le test à la P.T.C., les défauts de vision des couleurs, la latéralité, les mouvements de la langue, la pilosité inter-phalangienne ont été observés chez 75 hommes adultes de la communauté Dhimars du district de Mandla dans le Madhya Pradesh (Inde). Il s'agit d'un groupe endogame de pécheurs, porteurs de palanquin. Le polymorphisme de ces traits est étudié chez les Dhimars et l'affinité de ces populations avec d'autres populations est évaluée.Mastana Sarabjit S., Garg Rajeev. A study of morpho-behavioural and genetic traits among Dhimars of Mandla, Madhya Pradesh, India. In: Bulletins et Mémoires de la Société d'anthropologie de Paris, Nouvelle Série. Tome 2 fascicule 2, 1990. pp. 145-149

EPA/DHA dietary supplementation attenuates exercise-induced bronchoconstriction in physically active asthmatic males

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

A variant of position −308 of the Tumour necrosis factor alpha gene promoter and the risk of coronary heart disease

Purpose: The aim of this study was to investigate whether the variability between individuals with coronary heart disease (CHD) is related to the prevalence of TNF-α gene promoter −308 variant in un-matched British Caucasian population from East Midlands. Procedures: Genotypes and allele frequencies were determined using restriction fragment length polymorphism analysis of polymerase chain reaction (PCR) products. Genomic DNA prepared from peripheral blood leukocytes of patients (n = 97) and healthy controls (n = 95) demonstrated two alleles TNF*1 (G) and TNF*2 (A). Findings: The genotype distribution in patients was GG, n = 59; GA, n = 36; and AA, n = 2 and in controls was GG, n = 41; GA, n = 40; and AA, n = 14 (P = 0.014). The association analysis demonstrated that TNF*1 allele in patients appears to be associated with greater incidences of CHD (OR 2.15; CI, 1.36–3.39; P = 0.001). Conclusions: Our results suggest that TNF*1 allele (TNF-α −308 GG or GA) has a high prevalence among British Caucasian population that correlates with an increased CHD risk

Advances and challenges in thyroid cancer: the interplay of genetic modulators, targeted therapies, and AI-driven approaches

Thyroid cancer continues to exhibit a rising incidence globally, predominantly affecting women. Despite stable mortality rates, the unique characteristics of thyroid carcinoma warrant a distinct approach. Differentiated thyroid cancer, comprising most cases, is effectively managed through standard treatments such as thyroidectomy and radioiodine therapy. However, rarer variants, including anaplastic thyroid carcinoma, necessitate specialized interventions, often employing targeted therapies. Although these drugs focus on symptom management, they are not curative. This review delves into the fundamental modulators of thyroid cancers, encompassing genetic, epigenetic, and non-coding RNA factors while exploring their intricate interplay and influence. Epigenetic modifications directly affect the expression of causal genes, while long non-coding RNAs impact the function and expression of micro-RNAs, culminating in tumorigenesis. Additionally, this article provides a concise overview of the advantages and disadvantages associated with pharmacological and non-pharmacological therapeutic interventions in thyroid cancer. Furthermore, with technological advancements, integrating modern software and computing into healthcare and medical practices has become increasingly prevalent. Artificial intelligence and machine learning techniques hold the potential to predict treatment outcomes, analyze data, and develop personalized therapeutic approaches catering to patient specificity. In thyroid cancer, cutting-edge machine learning and deep learning technologies analyze factors such as ultrasonography results for tumor textures and biopsy samples from fine needle aspirations, paving the way for a more accurate and effective therapeutic landscape in the near future.</p

Genetic variation of MHC Class I polymorphic <i>Alu</i> insertions (POALINs) in three sub-populations of the East Midlands, UK

<p><b>Background:</b><i>Alu</i> elements are highly researched due to their useful nature as markers in the study of human population genetics. Recently discovered Major Histocompatibility Complex (MHC) polymorphic <i>Alu</i> insertions (POALINs) have not been examined extensively for genetic variation and their HLA associations.</p> <p><b>Aims:</b> The aim of this study is to assess the genetic variation between three populations using five recently discovered POALINs.</p> <p><b>Methods and subjects:</b> The study examined 190 healthy, unrelated subjects from three different populations in the East Midlands (UK) for the presence or absence of five <i>Alu</i> elements (<i>Alu</i>HG, <i>Alu</i>MICB, <i>Alu</i>HJ, <i>Alu</i>TF and <i>Alu</i>HF) via the polymerase chain reaction followed by gel electrophoresis. Data were analysed for genetic variation and phylogenetic analyses.</p> <p><b>Results:</b> All <i>Alus</i> were polymorphic in study populations. Appreciable allele frequency variation was observed at a number of loci. The British population was significantly different from both the Punjabi Jat Sikh and Gujarati Patel populations, although showing a closer genetic relationship to the Punjabi Jat Sikh population than the Gujarati Patel population (Nei’s D_A = 0.0031 and 0.0064, respectively).</p> <p><b>Conclusions:</b> MHC POALINs are useful markers in the investigation of genetic variation and the assessment of population relationships, and may have some bearing on disease associations due to their linkage disequilibrium with HLA loci; this warrants further studies.</p