Polygenic Condition Research Articles

EFFECTIVE AYURVEDIC APPROACH IN THE MANAGEMENT OF PCOS: A CASE REPORT

Nowadays, cases of Polycystic Ovarian Syndrome (PCOS) are rising very significantly, generally present in younger age groups due to faulty food habits, lifestyle, stress, etc. PCOS is a disease characterised by menstrual irregularities, elevated androgen levels and multiple cysts on one or both ovaries. A complex process is maintained by the intact uterine-adnexa and the hypothalamic-pituitary-ovarian axis in the female reproductive system. The normal functioning of the human body depends on the interdependence of all its systems, and any imbalance in one can lead to multisystem pathology. It is a common endocrinopathy, a multifactorial and polygenic condition resulting in anovulation or oligo-ovulation. In Ayurvedic classics, clinical features present in PCOS can be co-related with Pushpaghni Jataharini, Artavakshaya and Gulma roga. A 25-year-old female visited the OPD with complaints of irregular menstrual cycle, pimples and hair loss from the last six months. USG revealed Bilateral polycystic ovarian morphology. Oral administrations of shamana aushadhi have been done for three months. Regular menstrual cycles, along with improvements in symptoms, have been observed. Evidence for the complete cure of PCOS has produced an intriguing and positive outcome for researchers and professionals in this sector by following the principle of Gulma chikitsa. Shamana aushadhi, like Kanchanara Guggulu, Vriddhivadhika vati, Kumaryasava and Pathya churna, have shown excellent results in managing Polycystic Ovarian Syndrome.

The role of gut microbiota in the obesity: a literature review

Introduction: Obesity is a multifactorial and polygenic condition that, according to the World Obesity Federation, will affect over 1 billion people by 2030. In this regard, research is being conducted regarding gut microbiota influence on the pathogenesis of this disease, such as inflammation and insulin resistance. Therefore, understanding the gut microbiota and the mechanism by which its modulation through diet and/or the use of probiotics can impact the host and contribute to the treatment of obesity is essential. Methods: A systematic review was conducted on the PubMed, Scielo, and ScienceDirect databases, following the PRISMA protocol, from January 2018 to September 2022. Results and Conclusion: 415 articles were found. 36 studies were evaluated, and 20 were included in this review. The use of calorierestricting diets, along with the consumption of grains and cereals, was found to be useful in reducing strains that promote inflammation and insulin resistance, factors that are associated with obesity pathogenesis, leading to weight reduction. Other studies examined probiotics use, which led to lipopolysaccharides and insulin resistance reduction, as well as a decrease in the quantity of pro-inflammatory cytokines associated with obesity and type 2 diabetes mellitus. Therefore, combining diets with probiotic therapies may be a strategy for microbiota modulation, aiming to reduce inflammatory markers and insulin resistance.

The signaling pathways in obesity-related complications.

Obesity, a rapidly expanding epidemic worldwide, is known to exacerbate many medical conditions, making it a significant factor in multiple diseases and their associated complications. This threatening epidemic is linked to various harmful conditions such as type 2 diabetes mellitus, hypertension, metabolic dysfunction-associated steatotic liver disease, polycystic ovary syndrome, cardiovascular diseases (CVDs), dyslipidemia, and cancer. The rise in urbanization and sedentary lifestyles creates an environment that fosters obesity, leading to both psychosocial and medical complications. To identify individuals at risk and ensure timely treatment, it is crucial to have a better understanding of the pathophysiology of obesity and its comorbidities. This comprehensive review highlights the relationship between obesity and obesity-associated complications, including type 2 diabetes, hypertension, (CVDs), dyslipidemia, polycystic ovary syndrome, metabolic dysfunction-associated steatotic liver disease, gastrointestinal complications, and obstructive sleep apnea. It also explores the potential mechanisms underlying these associations. A thorough analysis of the interplay between obesity and its associated complications is vital in developing effective therapeutic strategies to combat the exponential increase in global obesity rates and mitigate the deadly consequences of this polygenic condition.

Serotonin-related Mechanisms in the Etiology and Pharmacotherapy of Social Phobia, A Review.

Social anxiety disorder (SAD), known as social phobia, is considered a prevalent psychiatric disorder characterized by a constant fear of social positions. Frequently, social phobia occurs with other mental disorders including depression and substance abuse conditions. Although SAD is considered one of the most common types of mental disorders, proper management may be compromised in recurrent psychiatric comorbidity due to clinicians' focus on secondary complications. Moreover, despite the description of social phobia as a polygenic and complex condition, few altered genetic and epigenetic factors are identified as causative agents. Over the past decades, several studies have suggested polymorphisms in serotonergic and dopaminergic-related genes as the etiology of social phobia. Serotonin, on the other hand, as a necessary neurotransmitter in the central nervous system (CNS), is involved in a variety of disease processes including social phobia. Nevertheless, the exact mechanism of serotonin-dependent development of the disease and the efficacy of suggested pharmacotherapies are not fully understood. The current study aimed to review the serotonin-dependent mechanisms by which SAD develops and discuss the current suggested strategies that are based on serotonin metabolism.

MTHFR, NR3C1, FKBP5, and CRHR1 gene polymorphisms are strongly associated with depressive disorder susceptibility: A meta-analysis and power analysis

Depression is a polygenic and complex condition; however, most genetic analyses have yielded insignificant associations between candidate genes and depressive disorder. This is primarily due to the lack of reproducible findings in genome-wide association studies (GWAS). In this meta-analysis, we extensively investigated the implications of genetic polymorphisms in seven candidate genes for depression. We conducted a thorough search of electronic databases, including Google Scholar, Cochrane, PubMed, Medline, Embase, and PsycINFO, covering data from January 1997 to 2022. Our search identified approximately 3,500 published research papers related to this study. Among these, 81 studies met our eligibility criteria and focused on the six genes under study. These selected candidate genes for our meta-analysis included NR3C1, MTHFR, FKBP5, CRHR1, COMT, and TNF-α. The results of our meta-analysis on genetic polymorphisms indicate a significant association with depression at the 95% confidence interval (CI). When categorizing outcomes by different ethnic groups, our findings reveal significant results (p=<0.05) for Asian and Caucasian populations. This current meta-analysis provides valuable insights that can facilitate the use of these significantly associated genes for diagnosing the severity of depression or as indicators for treatment modalities in depression conditions.

ROLE OF YOGABHYASA IN MANAGEMENT OF PCOD (POLYCYCSTIC OVARIAN SYNDROM)

Polycystic ovarian syndrome (PCOD) was originally described in 1935 by stein and leventhal as a syndrome manifested my amenorrhoea, hirsutism and obesity associated with enlarged. This heterogeneous disorder is characterised by excessive androgen production by the ovaries mainly. PCOS is a multifactorial and polygenic condition. Diagnosis is based upon the presence of any two of the following three criteria, oligo and / or anovulation, Hyperandrogenism, polycystic ovaries PCOS is characterized by chronic anovulation and hyperandrogenism in the absence of underlying adrenal or pituitary disease. Women with PCOS may complain about variable clinical manifestations loss including oligomenorrhoea, hirsutism, acne and infertility. The most preferred and effective method of treatment of PCOS is lifestyle modification. Weight loss is an important treatment strategy. Yoga is a complete prescription for the healthy body and mind which can destroy the root cause of PCOS which is obesity and stress, ultimately leads to better quality of life, Yogasanas promotes hormonal balance and deep relaxation helping to bring the adrenal and cortisol levels of stressed out PCOS minds and bodies in check. Yogasanas stimulates energy systems within the body. Yogasanas helps to stimulate the functions of the reproductive organs, relieves menstrual discomfort and normalizes the menstrual cycle, increases blood flow to the reproductive organs and enhances the functions of the ovaries.

Alterations of the Sialylation Machinery in Brugada Syndrome

Brugada Syndrome (BrS) is an inherited arrhythmogenic disorder with an increased risk of sudden cardiac death. Recent evidence suggests that BrS should be considered as an oligogenic or polygenic condition. Mutations in genes associated with BrS are found in about one-third of patients and they mainly disrupt the cardiac sodium channel NaV1.5, which is considered the main cause of the disease. However, voltage-gated channel's activity could be impacted by post-translational modifications such as sialylation, but their role in BrS remains unknown. Thus, we analyzed high risk BrS patients (n = 42) and healthy controls (n = 42) to assess an involvement of sialylation in BrS. Significant alterations in gene expression and protein sialylation were detected in Peripheral Blood Mononuclear Cells (PBMCs) from BrS patients. These changes were significantly associated with the phenotypic expression of the disease, as the size of the arrhythmogenic substrate and the duration of epicardial electrical abnormalities. Moreover, protein desialylation caused a reduction in the sodium current in an in vitro NaV1.5-overexpressing model. Dysregulation of the sialylation machinery provides definitive evidence that BrS affects extracardiac tissues, suggesting an underlying cause of the disease. Moreover, detection of these changes at the systemic level and their correlation with the clinical phenotype hint at the existence of a biomarker signature for BrS.

Promise of Physiological Profiling to Prevent Stroke in People of African Ancestry: Prototyping Ghana.

Worldwide, compared to other racial/ethnic groups, individuals of African ancestry have an excessively higher burden of hypertension-related morbidities, especially stroke. Identifying modifiable biological targets that contribute to these disparities could improve global stroke outcomes. In this scoping review, we discuss how pathological perturbations in the renin-angiotensin-aldosterone pathways could be harnessed via physiological profiling for the purposes of improving blood pressure control for stroke prevention among people of African ancestry. Transcontinental comparative data from the USA and Ghana show that the prevalence of treatment-resistant hypertension among stroke survivors is 42.7% among indigenous Africans, 16.1% among African Americans, and 6.9% among non-Hispanic Whites, p < 0.0001. A multicenter clinical trial of patients without stroke in 3 African countries (Nigeria, Kenya, and South Africa) demonstrated that physiological profiling using plasma renin activity and aldosterone to individualize selection of antihypertensive medications compared with usual care resulted in better blood pressure control with fewer medications over 12months. Among Ghanaian ischemic stroke survivors treated without renin-aldosterone profiling data, an analysis revealed that those with low renin phenotypes did not achieve any meaningful reduction in blood pressure over 12months on 3-4 antihypertensive medications despite excellent adherence. For a polygenic condition such as hypertension, individualized therapy based on plasma renin-aldosterone-guided selection of therapy for uncontrolled BP following precision medicine principles may be a viable strategy for primary and secondary stroke prevention with the potential to reduce disparities in the poor outcomes of stroke disproportionately shared by individuals of African ancestry. A dedicated clinical trial to test this hypothesis is warranted.

Precision Medicine in Type 2 Diabetes

Precision medicine is an innovative approach to tailoring disease prevention and treatment that takes into account differences in people’s genes, environments, and lifestyle patterns. The aim of such an approach is to lead a shift in the clinical treatment paradigm from a trial-and-error or perceptive approach to the right drug, for the right patient, at the right time. The characterization of human biology and behaviors is now possible at scale owing to advances in biomarkers, bioimaging, and wearable technologies. In addition, big data from electronic medical records, health insurance databases, and other platforms have become available. These have enabled the generation of new insights into the phenotype known as diabetes. Precision medicine in diabetes (PMD) refers to an approach to optimize the diagnosis, prediction, and prevention or treatment of diabetes by integrating multi-dimensional data accounting for individual differences. The potential for precision treatment in diabetes is vast and should be considered cost-effective. Compared to precision medicine of monogenic diabetes, precision medicine of type 2 diabetes is difficult due to the polygenic condition in which environment as well as thousands of etiological genetic variants play an important role. Although there are the great concerns about PMD, which is complex and difficult to do, is required much time, we look forward to clinical utility in the treatment of patients based on their effects on different classes of markers, including race, metabolic status, other phenotypic markers, and omics data for each class of antihyperglycemic medication in the near future.

A study of Heart Rate Variability (HRV) in healthy offsprings with parental history of type 2 diabetes mellitus

Introduction: Type 2 diabetes mellitus (T2DM) is a heterogeneous polygenic metabolic disease condition that is caused by insulin resistance leading to hyperglycemia. Since, T2DM is genetically inherited and autonomic dysfunction is its major complications, healthy offsprings of diabetic parents are highly vulnerable to manifest dysautonomia leading to insulin resistance.&#x0D; Objectives: We aimed to assess cardiac autonomic function using heart rate variability (HRV) parameters in healthy offsprings having parental history of T2DM.&#x0D; Methodology: A comparative cross-sectional study was carried out in the laboratory of department of Physiology enrolling 30 healthy offsprings of non-diabetic parents (Group 1) and 30 healthy offsprings of diabetic parents (Group 2). Anthropometric, biochemical and cardiovascular variables were assessed using standard procedures. Time domain and frequency domain parameters of HRV spectrum were assessed using photoplethysmography principle.&#x0D; Results: HRV findings revealed that markers of sympathetic regulation were significantly higher and those of parasympathetic function were significantly reduced in subject group having parental history of T2DM. LF/HF ratio was significantly increased suggesting sympatho-vagal imbalance in offspring of diabetic parents even in their euglycemic state.&#x0D; Conclusion: Alteration of cardiovascular autonomic function is found in healthy offspring of diabetic parents, characterized by reduced vagal activity and pronounced sympathetic regulation. Assessment of cardiac autonomic function would help in timely detection of such dysautonomia and reducing the life-threatening effects on offspring having parental history of T2DM.

Genetic variations in NLRP1 and Glutathione S-Transferase are associated with Generalized Vitiligo of Phlegmatic Clinical Phenotypes in Unani Medicine Philosophy of South Indian Population

Background: Generalized vitiligo is a common, multifaceted, polygenic condition in which autoimmune loss of melanocytes results in depigmented skin patches, overlying hair and mucous membranes. NLRP1 has been proposed to be implicated in the susceptibility of a broad variety of autoimmune disorders, including generalized vitiligo (GV). Genetic polymorphisms in the NLRP1 encoding gene (formerly known as NALP1) have previously been found to be linked with GV and there is uncertainty as to their role in the modulation of NLRP1 expression. Oxidative stress is a significant pathogenesis theory for vitiligo. Glutathione S-transferases (GSTs) are enzymes active in the defense of cells against chemical toxicity and stress.This study validates some of the Unani concepts of humors or temperaments (Phenotypes), with regard to Vitiligo, Where vitiligo is regarded as a phlegmatic disease. We selected Vitiligo subjects with Phlegmatic Clinical Phenotype for our study, with an aim to determine its association with the genetic biomarkers- NLRP1, GSTM1 and GSTT1 null genotypes and other biochemical parameters. Methods: The Unani clinicians randomly selected 100 vitiligo patients with a phlegmatic Clinical Phenotype who were attending NRIUMSD for treatment and 100 healthy volunteers belonging to Phlegmatic (Phlegmatic clinical Phenotype). Besides looking at temperaments/ humors as susceptibility factors – we included a genetic factor- NLRP1, GSTM1- and GSTT1-null genotypes to our investigation. We have genotyped the NLRP1, GSTM1- and GSTT1-null genotypes by PCR-RFLP and by Multiplex PCR, GST protein level estimation by ELISA method. Results: NLRP1 rs2670660 polymorphism was shown to be in significant association with GV, with the presence of minor alleles in active GV. We found that the frequencies of GSTM1 null genotype and GSTT1 null genotype in vitiligo patients were significantly high compared to the controls (OR= 1.47, 95% CI=0.765--2.861), (OR = 4.75, 95% CI = 2.131-10.63), respectively. In combination analysis with both genes, the results suggested significant association of vitiligo risk with both GSTM1\GSTT1 null genotypes (OR=4.83, 95% CI=1.523– 15.32).We observed a significant decrease (p&lt;0.001) in GST protein levels. Conclusion: Our findings indicate that NLRP1 rs2670660 polymorphism may be genetic risk factor for susceptibility to GV and the null genotypes of GSTM1 and GSTT1 of both genes increase the risk of the disease. A significant decrease (p&lt;0.001) in GST protein levels appeared to be a key feature in Vitiligo subjects, Therefore, detection of antioxidant enzyme levels can be effective biomarkers for early detection of the disease. We believed that GSTM1-and GSTT1-null genotype polymorphisms were associated with an increased risk of vitiligo. This is the first study of its kind along with Clinical Phenotype as per Unani Philosophy.

Human Resistin as a Marker to Monitor Lupus Nephritis and Atherosclerotic Changes in Females with SLE

Systemic lupus erythematosus (SLE) is a polygenic chronic inflammatory condition that influences several body organs. While renal and dermatological changes are among the most common presentations of the disease. The current study examines the possible association between human Resistin (h-Res) and signs of disorder activities such as inflammation, renal function, lipids, and Bone Mineral Density (BMD) in females with SLE. We performed cross-sectional research on 50 females with SLE diagnosed using the American College of Rheumatology (ACR) criteria. Forty females were recruited as controls. They matched the following items, including gender and body mass index (BMI) with age. In SLE patients, we discovered a statistically significant positive relationship between h-Res levels and ESR, CRP, Cr, ds-DNA, C3, duration of steroid treatment, and other variables. Disorder activity as determined by systemic lupus erythematosus disease index (SLEDAI) and carotid intima-media thickness (CIMT) (p-value &lt;0.05). The levels of h-Res and C3 are discovered to have a statistically significant negative relationship. In the case of SLE, the h-Res level can be used as a marker for Lupus Nephritis (LN) and atherosclerosis. In patients of SLE, more aggressive therapy of the underlying inflammatory process and better control of the traditional risk factors may be beneficial in reducing the risk of renal and atherosclerotic derangement. Keywords. biomarker, lupus nephritis, systemic lupus erythematous, Atherosclerosis

Association of Angiotensin II Type 1 Receptor (AT1R) Gene Polymorphism with Angiotensin II Serum Levels in Patients with Essential Hypertension.

Essential hypertension (EH) is a multifactorial, polygenic condition, and is one of the most important comorbidities that contributes to stroke, myocardial infarction, cardiac failure, and renal failure. The continuous increasing rate of morbidity and mortality associated with EH presents an unmet need of population-based studies to explore pathophysiology as well as newer strategies for better diagnosis, prognosis and treatment. This study aimed to determine genotype and allele frequencies of A1166C polymorphism of AT1R gene in Indian patients with EH and correlated with serum levels of Angiotensin II. A total of 200 patients with EH and 200 age- and gender-matched control individuals were included in this study from the General Medicine Department Outpatient at Narayana Medical College and Hospital, Nellore, Andhra Pradesh, India. Patients with systolic blood pressure (SBP) ≥ 140mmHg and/or diastolic blood pressure (DBP) ≥ 90mmHg were considered as hypertensive. The findings of this study revealed significantly increased risk of C/A heterozygote and allele C in both men and women. Moreover, both men and women patients with EH showed higher serum levels of Angiotensin II with C/A as well as AA genotypes. These findings indicate a significant association of 1166 C/A polymorphism of the AT1R gene with increased risk of hypertensionin Indian population.

Evaluation of serum proteome from Indian psoriasis patients.

Psoriasis is a polygenic chronic skin condition, associated with many systemic disorders. Though it is most studied dermatological condition, molecular mechanism leading to its pathogenesis is still unclear. An insight into its proteome may help unrevealing some biomarkers and therapeutic targets. In this study, we carried out mass spectrometry based quantitative proteomic analysis of serum from psoriasis patients by employing Tandem Mass Tags (TMT) approach. We identified 861,887 MS/MS spectra corresponding to 493 proteins. These dysregulated proteins were further classified by Gene Ontology and protein-protein interaction of dys-regulated proteins revealed networks in psoriasis patients.

Paediatric Behçet’s Disease: A Comprehensive Review with an Emphasis on Monogenic Mimics

Behçet’s disease (BD) is a polygenic condition with a complex immunopathogenetic background and challenging diagnostic and therapeutic concepts. Advances in genomic medicine have provided intriguing insights into disease pathogenesis over the last decade, especially into monogenic mimics of BD. Although a rare condition, paediatric BD should be considered an important differential diagnosis, especially in cases with similar phenotypes. Emerging reports of monogenic mimics have indicated the importance of genetic testing, particularly for those with early-onset, atypical features and familial aggregation. Treatment options ought to be evaluated in a multidisciplinary setting, given the complexity and diverse organ involvement. Owing to the rarity of the condition, there is a paucity of paediatric trials; thus, international collaboration is warranted to provide consensus recommendations for the management of children and young people. Herein, we summarise the current knowledge of the clinical presentation, immunopathogenetic associations and disease mechanisms in patients with paediatric BD and BD-related phenotypes, with particular emphasis on recently identified monogenic mimics.

Whole-Exome Sequencing in 10 Unrelated Patients with Syndromic Hidradenitis Suppurativa: A Preliminary Step for a Genotype-Phenotype Correlation

Background: The genetics of syndromic hidradenitis suppurativa (HS), an immune-mediated condition associated with systemic comorbidities such as inflammatory bowel diseases and arthritis, has not been completely elucidated. Objective: To describe clinical features and genetic signature of patients with the main syndromic HS forms, i.e., PASH, PAPASH, and PASH/SAPHO overlapping. Methods: Whole-exome sequencing (WES) approach was performed in ten patients with syndromic HS. Results: Three clinical settings have been identified based on presence/absence of gut and joint inflammation. Four PASH patients who had also gut inflammation showed three different variants in NOD2 gene, two variants in OTULIN, and a variant in GJB2, respectively. Three PAPASH and three PASH/SAPHO overlapping patients who had also joint inflammation showed two different variants in NCSTN, one in WDR1 and PSTPIP1, and two variants in NLRC4, one of whom was present in a patient with a mixed phenotype characterized by gut and joint inflammation. Limitations: Limited number of patients that can be counterbalanced by the rarity of syndromic HS. Conclusion: Syndromic HS can be considered as a polygenic autoinflammatory condition; currently WES is a diagnostic tool allowing more accurate genotype-phenotype correlation.

Research Progress on Epigenetics of Diabetic Cardiomyopathy in Type 2 Diabetes

Diabetic cardiomyopathy (DCM) is characterized by diastolic relaxation abnormalities in its initial stages and by clinical heart failure (HF) without dyslipidemia, hypertension, and coronary artery disease in its last stages. DCM contributes to the high mortality and morbidity rates observed in diabetic populations. Diabetes is a polygenic, heritable, and complex condition that is exacerbated by environmental factors. Recent studies have demonstrated that epigenetics directly or indirectly contribute to pathogenesis. While epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, have been recognized as key players in the pathogenesis of DCM, some of their impacts remain not well understood. Furthering our understanding of the roles played by epigenetics in DCM will provide novel avenues for DCM therapeutics and prevention strategies.

A Case Study on Ayurvedic Management in PCOS

Female reproductive system consists of hypothalamo-pituitary-ovarian axis and intact uterine-adnexa which maintains a complex mechanism. In human body all the systems are interrelated to function properly; any imbalance in one system may cause multisystem pathogenesis. Polycystic ovarian syndrome (PCOS) is a common endocrinopathy, which is multifactorial and polygenic condition, manifested as oligoovulation or anovulation, signs of hyperandrogenism and multiple small ovarian cysts. Signs and symptoms vary within individual’s overtime. This adversely affect the reproductive system by menstrual disorders, infertility, obesity, depression, sleep apnea, insulin resistance and in due course may result in diabetes mellitus, endometrial cancer, cardiovascular disease etc. According to Ayurveda PCOS is a disorder which involves the three Doshas, Dhathus like Rasa, Raktha and Medas. The Srothas involved in this condition are Rasa, Rakta and Arthava vaha which eventually manifests features such as Anarthava (amenorrhea), Vandhyathwa, Pushpagni, Abeeja rtuchakra (anovular bleeding). Here is a case report of 19 year old girl who presented with irregular menstruation, rapid weight gain and hair loss. On USG she was detected to have bilateral PCO pattern. Based on the clinical features, treatment principles adopted were Aamapachana, Vata anulomana, Kaphapittahara and Arthava janana. After 2 months of internal medications, symptoms reduced markedly and menstruation was normal. Adherence to Ayurvedic principles is found to be helpful in PCOS for a healthy and fruitful life.

Granzyme B gene polymorphism in vitiligo: does it have an association?

Objectives To study the role of granzyme B (GZMB) gene polymorphism (rs8192917) in patients with nonsegmental vitiligo and to correlate the results with the available clinical information. Background Vitiligo is considered the most common acquired disease of depigmented skin characterized by depigmented patches of the skin, hair, and mucous membranes owing to destruction of melanocytes. Vitiligo is a multifactorial polygenic condition with a multifaceted pathogenesis, linked to both genetic and nongenetic aspects, such as autoimmune, cytotoxic, oxidant–antioxidant, and neural therories working in performance. Patients and methods GZMB gene polymorphism (rs8192917) was identified using real-time PCR technique in 40 patients having nonsegmental vitiligo and 40 age-matched and sex-matched healthy controls. Assessment of disease severity was done using Vitiligo Area Severity Index score, and disease activity was assessed using Vitiligo Disease Activity score. Results CC and TC genotypes were significantly higher in the patients' group [P = 0.005; odds ratio (OR) = 7.2, 95% confidence interval (CI) = 1.61–32.2 for CC and OR = 1.86, 95% CI = 0.42–8.15 for TC], with significant statistical preponderance of C allele in cases (P = 0.001; OR = 3.05, 95% CI = 1.55–6.01). Conclusion GZMB gene polymorphism (rs8192917) is associated with the susceptibility to nonsegmental vitiligo in a sample of Egyptian population.

Genetics of Skeletal Disorders.

Bone and mineral diseases encompass a variety of conditions that involve altered skeletal homeostasis and are frequently associated with changes in circulating calcium, phosphate, or vitamin D metabolites. These disorders often have a genetic etiology and comprise monogenic disorders caused by a single-gene mutation, which may be germline or somatic, or an oligogenic or polygenic condition involving multiple genetic variants. Single-gene mutations causing Mendelian diseases are usually highly penetrant, whereas the gene variants contributing to oligogenic or polygenic disorders are each associated with smaller effects with additional contributions from environmental factors. The detection of monogenic disorders is clinically important and facilitates timely assessment and management of the patient and their affected relatives. The diagnosis of monogenic metabolic bone disorders requires detailed clinical assessment of the wide variety of symptoms and signs associated with these diseases. Thus, clinicians should undertake a systematic approach commencing with careful history taking and physical examination, followed by appropriate laboratory and skeletal imaging investigations. Finally, clinicians should be familiar with the range of molecular genetic tests available to ensure their appropriate use and interpretation. These considerations are reviewed in this chapter.