Phenotypic Polymorphism Research Articles

Dimerization of melanocortin 4 receptor controls puberty onset and body size polymorphism.

Xiphophorus fish exhibit a clear phenotypic polymorphism in puberty onset and reproductive strategies of males. In X. nigrensis and X. multilineatus, puberty onset is genetically determined and linked to a melanocortin 4 receptor (Mc4r) polymorphism of wild-type and mutant alleles on the sex chromosomes. We hypothesized that Mc4r mutant alleles act on wild-type alleles by a dominant negative effect through receptor dimerization, leading to differential intracellular signaling and effector gene activation. Depending on signaling strength, the onset of puberty either occurs early or is delayed. Here, we show by Förster Resonance Energy Transfer (FRET) that wild-type Xiphophorus Mc4r monomers can form homodimers, but also heterodimers with mutant receptors resulting in compromised signaling which explains the reduced Mc4r signaling in large males. Thus, hetero- vs. homo- dimerization seems to be the key molecular mechanism for the polymorphism in puberty onset and body size in male fish.

The genomics and evolution of inter-sexual mimicry and female-limited polymorphisms in damselflies

Sex-limited morphs can provide profound insights into the evolution and genomic architecture of complex phenotypes. Inter-sexual mimicry is one particular type of sex-limited polymorphism in which a novel morph resembles the opposite sex. While inter-sexual mimics are known in both sexes and a diverse range of animals, their evolutionary origin is poorly understood. Here, we investigated the genomic basis of female-limited morphs and male mimicry in the common bluetail damselfly. Differential gene expression between morphs has been documented in damselflies, but no causal locus has been previously identified. We found that male mimicry originated in an ancestrally sexually dimorphic lineage in association with multiple structural changes, probably driven by transposable element activity. These changes resulted in ~900 kb of novel genomic content that is partly shared by male mimics in a close relative, indicating that male mimicry is a trans-species polymorphism. More recently, a third morph originated following the translocation of part of the male-mimicry sequence into a genomic position ~3.5 mb apart. We provide evidence of balancing selection maintaining male mimicry, in line with previous field population studies. Our results underscore how structural variants affecting a handful of potentially regulatory genes and morph-specific genes can give rise to novel and complex phenotypic polymorphisms.

Genome-wide association study of health and production traits in meat sheep.

Genotypes are currently widely used in animal breeding programmes to enhance the speed of genetic progress. With sufficient data, a Genome-Wide Association Study (GWAS) can be performed to identify informative markers. The aim of this study was to investigate the genetic background of health (footrot and mastitis) and production (birth weight, weaning weight, scan weight, and fat and muscle depth) traits using the available phenotypic and Single Nucleotide Polymorphism (SNP) data collected on the UK Texel sheep population. Initially, 10193 genotypes were subject to quality control, leaving 9505 genotypes for further analysis. Selected genotypes, recorded on four different Illumina chip types from low density (15k SNPs) to high density (606006 SNPs), were imputed to a subset of 45686 markers from 50k array, distributed on 27 chromosomes. Phenotypes collected on 32 farms across the UK for footrot and mastitis and extracted from the UK National database (iTexel) for the production traits were used along with pre-estimated variance components to obtain de-regressed breeding values and used to perform GWAS. Results showed three SNPs being significant on the genome-wise level ('OAR8_62240378.1' on chromosome 8 for birth weight, 's14444.1' on chromosome 19 for weaning weight and 's65197.1' on chromosome 23 for scan weight). Fourteen subsequent SNPs were found to be significant at the chromosome-wise level. These SNPs are located within or close to previously reported QTLs impacting on animal health (such as faecal egg count or somatic cell count) and production (such as body or carcass weight and fat amount). These results indicate that the studied traits are highly polygenic with complex genetic architecture.

Prevalence of bronchial asthma and correlation between the chemokine receptor 3 gene polymorphism and clinical asthma phenotypes among Egyptian asthmatic children

BackgroundAsthma is a chronic inflammatory airway disease characterized by episodic reversible airway obstruction that variably presents with cough, wheezing, shortness of breath, or chest tightness. It is a multigenetic disease, where both genetic and environmental factors have significant roles in pathogenesis. As regard asthma pathogenesis, the chemokine/chemokine receptor system is considered a key point of the immune response in most allergic diseases. This study was done to estimate the prevalence of bronchial asthma among school age children and explore the association between the underlying gene polymorphisms in chemokine receptor 3 (CCR3) and symptom-based clinical asthma phenotypes among a cohort of Egyptian children.ResultsPrevalence of asthma is increasing (20.6%). There are male asthma predominance. Family history of bronchial asthma and allergic diseases are predominant risk factors for asthma development. Sixty asthmatic cases with different clinical phenotypes were compared to 100 healthy controls, results explored that eosinophilic percent and total serum IgE are significantly higher among asthmatic cases versus controls. There are no significant difference regarding eosinophilic percent, serum IgE, and CCR3 T51C gene polymorphism among different clinical asthma phenotypes. There is no significant difference as regards degree of severity of asthma and level of asthma control between CCR3 T51C gene polymorphism.ConclusionWe conclude the prevalence of bronchial asthma is increasing. Also, eosinophilic percent and serum IgE are elevated in asthma patients, while CCR3 T51C gene polymorphism frequency seemed to be more prevalent among asthmatic subjects however without statistical significance. We recommend a prospective study on larger sample size to validate our results.

Evaluation of the phenotypic polymorphism of the pattern of Leptinotarsa decemlineata Say pronotum in the conditions of Kamianka-Buzka city (Lviv Oblast)

Aim. The Colorado potato beetle population is characterized by a high degree of polymorphism. This provides a high level of adaptability to the most diverse distribution conditions. The aim is to the study of the variability of the pattern of Leptinotarsa decemlineata pronotum in June 2021 and June 2022. Methods. The analysis of the phenotypic variability of L. decemlineata population of Kamianka-Buzka city based on studying the presence or absence of certain phens, their number and placement according to Tauer method. Results. 22 variations of phens belonging to A, B, C, D, E, G, K, L, M, P groups were found. The dominant were phens of A, B, C, D, E, F groups. The most variable were the phens of A and E groups. The phenotypic structure of the colorado beetle population was determined according to Kohmaniuk’s classification. It was found that the dominant morphs in 2021 and 2022 were U (42 % and 27 %), UP (13 % and 18 %) and V (23 % and 21 %), respectively. Conclusions. The analysis of the frequency of phenoforms according to the Fasulati method showed that in the population of 2021 and 2022, phenoforms 3, 6 and 9 were dominant. They form the basis of the population and ensure the resistance of the population to the insecticides. The study of the intrapopulation diversity indicates an unbalanced population structure of L. decemlineata.

Pelvic spine reduction affects diet but not gill raker morphology in two polymorphic brook stickleback (Culaea inconstans) populations.

Pelvic spine polymorphism occurs in several species in the stickleback family (Gasterosteidae). Given the similar phenotypic polymorphisms in multiple stickleback species, we sought to determine the extent of parallelism in the ecological correlates of pelvic spine reduction. Based on a metabarcoding analysis of brook stickleback gut contents in two polymorphic populations, we found that significant diet differences were associated with pelvic spine reduction, but we found no clear or consistent trend supporting a tendency for benthic feeding in pelvic-reduced brook sticklebacks. These results contrast with those found in threespine sticklebacks where pelvic spine reduction is often associated with a benthic diet. Hence, we found non-parallel consequences of spine polymorphism across species. Furthermore, a difference in gill raker morphology has been frequently observed between ecomorphs with different diets in many fish species. However, we found no evidence of any difference in gill raker morphology associated with pelvic spine polymorphism in brook sticklebacks.

Phenotypic Polymorphism in Two Endosymbiotic Bacteria of the Ciliate Paramecium: Pseudolyticum multiflagellatum and “Ca. Megaira venefica”

Here, we report a comprehensive description of the stable associations between two Paramecium species (P. nephridiatum and P. caudatum) and their cytoplasmic bacterial endosymbiont Pseudolyticum multiflagellatum. These spindle-like, rod-shaped, non-motile peritrichous bacteria demonstrate significant phenotypic polymorphism. Considering the differences in bacterial morphology and host species, several scientific groups have previously described these endosymbionts as distinct species. Our study provides brand-new molecular data, which allows us to unify earlier descriptions and determine the phylogenetic position of this endosymbiont as a member of the family “Ca. Midichloriaceae” (Rickettsiales). The distinguishing feature of this bacterium is the presence of a highly refractive granule in its cytoplasm, well detectable with differential interference contrast (DIC) microscopy. The protein nature of these peculiar inclusion bodies is considered. The other endosymbiont, “Ca. Megaira venefica”, co-inhabiting the cytoplasm of the studied P. nephridiatum strains, also displayed polymorphism, rounded forms being infected with phages.

Combined genome-wide association studies and expression quantitative trait locus analysis uncovers a genetic regulatory network of floral organ number in a tree peony (Paeonia suffruticosa Andrews) breeding population.

Great progress has been made in our understanding of floral organ identity determination and its regulatory network in many species; however, the quantitative genetic basis of floral organ number variation is far less well understood for species-specific traits from the perspective of population variation. Here, using a tree peony (Paeonia suffruticosa Andrews, Paeoniaceae) cultivar population as a model, the phenotypic polymorphism and genetic variation based on genome-wide association studies (GWAS) and expression quantitative trait locus (eQTL) analysis were analyzed. Based on 24 phenotypic traits of 271 representative cultivars, the transcript profiles of 119 cultivars were obtained, which indicated abundant genetic variation in tree peony. In total, 86 GWAS-related cis-eQTLs and 3188 trans-eQTL gene pairs were found to be associated with the numbers of petals, stamens, and carpels. In addition, 19 floral organ number-related hub genes with 121 cis-eQTLs were obtained by weighted gene co-expression network analysis, among which five hub genes belonging to the ABCE genes of the MADS-box family and their spatial-temporal co-expression and regulatory network were constructed. These results not only help our understanding of the genetic basis of floral organ number variation during domestication, but also pave the way to studying the quantitative genetics and evolution of flower organ number and their regulatory network within populations.

Baló’s concentric sclerosis in the pediatric population: literature review and analysis of clinical cases in the context of follow up observation

Baló’s concentric sclerosis is a rare variant of atypical pseudotumor demyelination, having a pathogenetic similarity with multiple sclerosis and a characteristic neuroimaging pattern with relative clinical heterogeneity. In children and adolescents, Baló’s concentric sclerosis even rarer than in adults, is represented in the scientific literature by single descriptions of clinical cases with a polymorphic clinical phenotype and various anamnestic prerequisites (for example, infectious). Moreover, the published cases do not involve the analysis of a long-term clinical following up in children and adolescents with this pathology, possibly due to their transition to adult neurological services as they grow up. This sample does not allow the analysis of cases of Baló’s concentric sclerosis with pediatric debuts and answer questions about the clinical features and therapeutic needs for such patients. Especially a lot of questions have accumulated concerning approaches to the treatment of patients with the classical, mono-focal form of Baló’s concentric sclerosis. The lack of scientific and clinical information hinders the adoption of administrative decisions on prescribing drugs from the PITRS group (drugs that change the course of multiple sclerosis) to such patients. 
 To replenish the literature base of pediatric cases of Baló’s concentric sclerosis, we analyzed the Russian experience of long-term (from 2 to 6 years) curation of three juvenile patients with acute non-infectious demyelinating episode and monofocal concentric lesion of the white matter of the brain. Russian data demonstrate the long-term efficacy and tolerability of drugs from the PITRS group among pediatric patients with Baló’s concentric sclerosis.

Association between chemokine receptor 3T51C gene polymorphism and different clinical asthma phenotypes in Egyptian asthmatic children

Association between chemokine receptor 3T51C gene polymorphism and different clinical asthma phenotypes in Egyptian asthmatic children

Phenotypic polymorphism of African bony tongue fish Heterotis niloticus (Cuvier, 1829) in Cameroon rainforest region

The study on the phenotypic polymorphism of Heterotis niloticus was undertaken from February to May 2020 in the rain forest region of Cameroon. The main objective was to contribute to a better understanding of the genetic diversity of this adapted species for adequate breeding and preservation strategies. More specifically, the investigation aimed at evaluating the variability of phenotypic, morphometric and meristic features according to the study sites. Further, it was also in order to analyse the phenotypic variability, the structure, as well as the phylogenetic relationships among the Heterotis niloticus subpopulations. A total of 125 adult individuals were collected in three localities and characterized. Two (2) phaneroptic traits were observed, while 16 morphometric traits were measured and 5 meristic characters were counted. The results showed that there is a colour variability of eyes and body in Heterotis niloticus from the study area with a predominance of golden eyes (97.60%) and grey body (96.80%). The number of scales on the lateral line was higher in the individuals collected in Mbalmayo (38.67±1.46) than those in Ayos (37.70±0.95). Discriminant factor analyses and phylogenetic analyses revealed that the overall population studied is made up of 3 morphotypes cohabiting in the three localities; thus it was possible to establish the phylogenetic relationships that exist between them. Morphotypes 1 and 2 are closer while morphotypes 2 and 3 are far apart, showing a tendency of splitting genetic make up. The recorded diversity suggests that Heterotis niloticus from the study area constitutes a natural genetic resource having the interesting variability for further improvement and sustainable management.

Immune Checkpoint Glycoproteins Have Polymorphism: Are Monoclonal Antibodies Too Specific?

Since the 2018 Nobel prize in medicine was granted to the discovery of immune escape by cancer cells, billions of dollars have been spent on a new form of cancer immunotherapy called immune checkpoint inhibition (ICI). In this treatment modality, monoclonal antibodies (mAbs) are used to block cell-surface glycoproteins responsible for cancer immune escape. However, only a subset of patients benefit from this treatment. In this commentary, we focus on the polymorphism in the target molecules of these mAbs, namely PD-1, PD-L1 and CTLA4; we explain that using a single mAb from one clone is unlikely to succeed in treating all humans because humans have a genotype and phenotype polymorphism in these molecules. Monoclonal antibodies are highly specific and are capable of recognizing only one epitope ("monospecific"), which makes them ideal for use in laboratory animals because these animals are generationally inbred and genetically identical (isogenic). In humans, however, the encoding genes for PD-1, PD-L1 and CTLA4 have variations (alleles), and the final protein products have phenotype polymorphism. This means that small differences exist in these proteins among individual humans, rendering one mAb too specific to cover all patients. Our suggestion for the next step in advancing this oncotherapy is to focus on methods to tailor the mAb treatment individually for each patient or replace a single clone of mAb with less specific alternatives, e.g., a "cocktail of mAbs", oligoclonal antibodies or recombinant polyclonal antibodies. Fortunately, there are ongoing clinical trials on oligoclonal antibodies at the moment.

The Phenotypic Polymorphism of Saliva From Dental Caries Patients

Introduction: The tooth decay or dental caries is a disease that results in imbalance in mineralization process of the tooth, cavitation and sensitivity as well as pulp infection that leading to inflammation and eventually tooth loose. Saliva which is in direct contact with the dentine, can serve as a medium for analysis of components or factors that show the difference in normal healthy and disease conditions. Methodology: Here, a biochemical analysis of individual saliva samples from healthy control and caries patients were carried out to see the differences in protein profiles. The unstimulated saliva samples were analyzed through sodium dodecyl sulfate polyacrylamide gel (SDS-PAGE), two-dimensional gel electrophoresis (2D gel), zymography and secretary IgA (sIgA) antibody ELISA procedure. Results: Differences were observed in individual samples not only in polymorphic band pattern on SDS-PAGE gels but also in activity of proteases in the saliva and the concentration of sIgA antibody. Conclusion: These were the initial results obtained from the study that was further optimized and evaluated with accuracy and reported elsewhere with statistical figures.

The range-wide mitochondrial lineage of Natrix natrix scutata (Pallas, 1771) presented in the northern Zagros Mountains

Natrix natrix (Linnaeus, 1758) is a common species distributed from Central Europe to Central Asia. In this range, it forms four subspecies that include several mitochondrial evolutionary lineages. One of the lineages, the so-called mtDNA lineage 8, has a wide distribution from the Baltic area to Anatolia and Kazakhstan. In Anatolia, this lineage meets several others, however, their occurrence is unclear, especially in the south-eastern Türkiye where the species is uncommon. Obtaining one specimen from the poorly studied Hakkâri Province (Zagros part of Türkiye), we investigated its genetic affiliation (mitochondrial DNA) and basic morphology. The specimen represents a unique haplotype of the mtDNA lineage 8, closely related to populations from Georgia and northern and north-eastern Türkiye. It thus extends the occurrence of this mitochondrial lineage representing subspecies Natrix natrix scutata (Pallas, 1771) southward to the northern edge of the Zagros Mountains. Despite the phenotype polymorphism of this species, the morphological comparison also confirmed that selected characters are similar to other populations of the region.

Influence of Haptoglobin and Hemoglobin Phenotypic Polymorphisms on Sickle Cell Disease Morbidity

Influence of Haptoglobin and Hemoglobin Phenotypic Polymorphisms on Sickle Cell Disease Morbidity

Immunological and genetic predictors of breast cancer

Aim. To investigate the associations of idiotypic IgA antibodies against benzo[a]pyrene, estradiol and progesterone (IgA1 -Bp, IgA1 -E2, and IgA1 - Pg) with the corresponding anti-idiotypic IgG antibodies to estradiol and progesterone (IgG2 -E2 and IgG2 -Pg) and with gene polymorphisms of CYP1A1, CYP1A2, CYP1B1, CYP17A1, CYP19A1, GSTM1, GSTT1, and GSTP1 in patients with stage 1 breast cancer. Materials and Methods. Idiotypic and anti-idiotypic antibodies in the serum of 240 healthy women and 505 patients with stage 1 breast cancer were measured by enzyme-linked immunosorbent assay. Prevalence of CYP1A1 (rs4646903), CYP1A2 (rs762551), CYP1B1 (rs1056836), CYP19A1 (rs2470152), GSTM1(del), GSTT1(del), and GSTP1 (rs1695) polymorphisms in 530 healthy women and 694 patients with stage 1 breast cancer were determined by real-time polymerase chain reaction.Results. Low personal IgA1 -Bp/IgA1 -Pg < 1 and IgA1 -E2/IgA1 -Pg < 1 ratios in combination with low IgG2 -E2 ≤ 4 and high IgG2 -Pg > 2 levels were found in 20.6% of healthy women and in 4.5% of breast cancer patients (p < 0.0001; OR = 0.2). Low IgA1 -Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios in combination with low IgG2 -E2 and high IgG2 - Pg levels were revealed in 7.4% of healthy women and 2.8% of breast cancer patients (p = 0.009; OR = 0.4). These two variants were integrated and marked as protective immunological phenotype. High IgA1 - Bp/IgA1 -Pg and high IgA1 -E2/IgA1 -Pg ratios combined with high IgG2 -Pg and high or low IgG2 -E2 levels were found in 17.2% of healthy women and27.2% of breast cancer patients (p = 0.006; OR = 1.8) and in 6.4% of healthy women and in 18.3% of breast cancer patients (p < 0.0001; OR = 3.3), correspondingly. These two variants were integrated and marked as pro-carcinogenic immunological phenotype. These associations were found only with estrogen receptor-positive (ER+) breast cancer. GSTP1 (rs1695) gene polymorphism was associated exclusively with estrogen receptor-negative (ER-) breast cancer (p = 0.004; OR = 1.56). No interrelations be tween immunological phenotypes and studied polymorphisms of CYP and GST genes have been found.Conclusion. Pro-carcinogenic immunological phenotype and rs1695 gene polymorphism within the GSTP1 gene were independent predictors of ER+ and ER- breast cancer correspondingly.

Similar and Divergent Roles of Stringent Regulator (p)ppGpp and DksA on Pleiotropic Phenotype of Yersinia enterocolitica.

Stringent response plays an important role in the response of Enterobacteriaceae pathogens to rapid environmental changes. It has been shown that synergistic and antagonistic actions exist between the signaling molecules (p)ppGpp and DksA in several foodborne pathogens; however, the biological function of these molecules and their interactions in Yersinia are still unclear. This study systematically investigated the role of stringent response in Yersinia enterocolitica, a typical foodborne Enterobacteriaceae pathogen, by deleting the (p)ppGpp and DksA biosynthesis genes. (p)ppGpp and DksA copositively regulated most phenotypes, such as motility, antibiotic resistance, and tolerance to oxidative stress, whereas they exhibited independent and/or divergent roles in the growth and biofilm synthesis of Y. enterocolitica. Gene expression analysis revealed that (p)ppGpp- and DksA-deficiency reduced the transcription of flagellar synthesis genes (fliC and flgD) and biofilm synthesis genes (bssS and hmsHFRS), which could potentially contribute to changes in motility and biofilm formation. These results indicate that stringent response regulators (p)ppGpp and DksA have a synergistic role and independent or even completely opposite biological functions in regulating genes and phenotypes of Y. enterocolitica. Our findings revealed the biofunctional relationships between (p)ppGpp and DksA and the underlying molecular mechanisms in the regulation of the pathogenic phenotype of Y. enterocolitica. IMPORTANCE The synergetic actions between the stringent response signaling molecules, (p)ppGpp and DksA, have been widely reported. However, recent transcriptomic and phenotypic studies have suggested that independent or even opposite actions exist between them. In this study, we demonstrated that the knockout of (p)ppGpp and DksA affects the polymorphic phenotype of Yersinia enterocolitica. Although most of the tested phenotypes, such as motility, antibiotic resistance, and tolerance to oxidative stress, were copositively regulated by (p)ppGpp and DksA, it also showed inconsistencies in biofilm formation ability as well as some independent phenotypes. This study deepens our understanding of the strategies of foodborne pathogens to survive in complex environments, so as to provide theoretical basis for the control and treatment of these microorganisms.

Analyzying the documented results by using microscopic agglutination test to examine sera from patients suspected of leptospirosis

Leptospirosis holds one of the leading places among zoonoses due to the breadth of distribution of natural and economic foci, as well as the severity of the clinical manifestation and mortality rate. A relatively low incidence rate in some regions is usually accounted for by unsatisfactory level of differential diagnostics, including insufficient coverage by diagnostic tests. Leptospira are characterized by marked phenotypic and genotypic polymorphisms, affecting epidemiological features and clinical manifestation of leptospirosis. Therefore, laboratory methods are important tool for epidemiological surveillance and diagnostics of leptospirosis. Serological methods primarily the microscopic agglutination test (MAT) currently remain the leading tool in investigating leptospirosis. To study a near 60 year-long contribution of various leptospira serogroups to etiological pattern of leptospirosis, we have analyzed archived MAT serum data from patients suspected of leptospirosis retrieved from our laboratory journals during from the years 1962 to 2020. It was shown that antibodies to the Grippotyphosa serogroup (25.1%) were found most often in patients, which might be associated with the wide range of reservoir host animals and resistance of this leptospira serogroup to environmental factors. At the same time, it should be noted that at different periods antibodies to various leptospira serogroups prevailed in the sera of patients, and in many cases this data matched with the contribution of these pathogens to the etiological morbidity pattern. In particular, dominance of pathogens of the Sejroe serogroup is currently the global trend in the etiological pattern of leptospirosis that was also observed by us at some years. The data obtained might be useful for epidemiological surveillance of leptospirosis infection, including predicting potential outbreaks, as well as for developing approaches to its diagnostics, treatment and prevention.

Association of Myostatin Gene Polymorphisms with Strength and Muscle Mass in Athletes: A Systematic Review and Meta-Analysis of the MSTN rs1805086 Mutation.

Polymorphism (rs1805086), c.458A>G, p.Lys(K)153Arg(R), (K153R) of the myostatin gene (MSTN) has been associated with a skeletal muscle phenotype (hypertrophic response in muscles due to strength training). However, there are not enough reliable data to demonstrate whether MSTN rs1805086 K and R allelic variants are valid genetic factors that can affect the strength phenotype of athletes' skeletal muscles. The aim is to conduct a systematic review and meta-analysis of the association of MSTN rs1805086 polymorphism with the strength phenotype of athletes. This study analyzed 71 research articles on MSTN and performed a meta-analysis of MSTN K153R rs1805086 polymorphism in strength-oriented athletes and a control (non-athletes) group. It was found that athletes in the strength-oriented athlete group had a higher frequency of the R minor variant than that in the control group (OR = 2.02, P = 0.05). Thus, the obtained results convincingly demonstrate that there is an association between the studied polymorphism and strength phenotype of athletes; therefore, further studies on this association are scientifically warranted.

187P BUB1 (2530C>T) polymorphism and expression affects chemotherapy response and predicts poor prognosis in advanced epithelial ovarian cancer

Ovarian cancer (OC) is a frequent gynecological cancer with a complex pathophysiology and high mortality. This study determines roles of 2530C>T SNP in BUB1, a key component of spindle assembly checkpoint (SAC), and its expression in advanced OC pathology & treatment outcome. 77 advanced epithelial OC patients were recruited, who received postoperative adjuvant [I.V. doses of 175mg/m2 paclitaxel+ carboplatin AUC 5-6mg.min/mL] or neoadjuvant chemotherapy with interval debulking surgery. Their demographics, clinical parameters, toxicity and survival were recorded. BUB1(2530C>T) SNP was detected by the PCR-RFLP followed by sequencing. BUB1 expression, BUB1mRNA and miRNA-495 were assessed using IHC & qRT-PCR. Stages III (82·02%) and IV (17·98%) OC patients were mostly 41-60 (60%) years old. 37%, 40%, 23%% were categorized as responders (Rs), partial responders (PRs) and non-responders (NRs) with significantly different (p<0.05) survival outcomes. The polymorphic homozygous genotypes (CC) and (TT) of 2530C>T were most prevalent in NRs & PRs respectively showing significant association in chemotherapy response (p=0.021). The allele frequencies were found to be C= 0.2215, and T= 0.7784. The standard regimen was well tolerated but no significant relationship was observed between SNP and toxicities. The survival outcome was nearly significant (p= 0.06) showing association of CC genotype with higher risk (HR=9.938, 95%CI= 1.19-82.9) when compared to CT (HR=0.885, 95%CI= 0.109-7.19) and TT (HR=0.409, 95%CI= 0.049-2.209). 97.6% of biopsy samples showed low to moderate BUB1 IHC expression and did not have significant association with clinical response (p=0.32). BUB1 mRNA and miR-495 analysis revealed a Ct mean of 37.42 and 27.614 respectively. There was a negative correlation between BUB1mRNA and miR-495 levels (r= -0.551, p=0.16). The homozygous polymorphic phenotypes of 2530C>T are significantly associated with chemotherapy response and poor survival outcomes but not related to chemo-induced toxicity. The very low expression of BUB1 may be attributed to regulation by miR-495. The negative expression also suggests a deficient SAC response in the advanced tumour.