The HBG2 rs7482144 (C > T) Polymorphism is Linked to HbF Levels but not to the Severity of Sickle Cell Anemia.

Sickle cell anemia (SCA) is a severe disease characterized by anemia, acute clinical complications, and a relatively short life span. In this disease, abnormal hemoglobin makes the red blood cells deformed, rigid, and sticky. Fetal hemoglobin (HbF) is one of the key modulators of SCA morbidity and mortality. Interindividual HbF variation is a heritable trait that is controlled by polymorphism in genes linked and unlinked to the hemoglobin ß gene (HBB). The genetic polymorphisms that determine HbF levels are known to ameliorate acute clinical events. About 190 well-characterized homozygous SCA patients were included in this study. Complete blood count (CBC), high-performance liquid chromatography (HPLC), and clinical investigations were obtained from patient's records. Severity scores were determined by using the combination of anemia, complications, total leucocyte count, and transfusion scores. HBG2 rs7482144 polymorphism was genotyped by using the polymerase chain reaction and restriction fragment length polymorphism. The association between HBG2 rs7482144 polymorphism and HbF levels as well as the disease severity of SCA were assessed. SCA patients carrying TT genotype were found to have higher HbF levels. In addition, SCA patients with increased severity showed significantly lower levels of hemoglobin, HbF, and hematocrit values. However, the genotypes of HBG2 rs7482144 polymorphism were not found to be associated with the risk of disease severity. In summary, this study demonstrated that HBG2 rs7482144 polymorphism is linked with HbF levels, but it does not affect disease severity. The sample sizes used and the pattern of association deduced from our small sample size prevents us from extrapolating our findings further.

Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases.

Cardiovascular disease (CVD) is a broad term that incorporated a group of conditions that affect the blood vessels and the heart. CVD is a foremost cause of fatalities around the world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays a vital role in generating reactive oxygen species (ROS). Oxidative stress occurs when the concentration of oxidants exceeds the potency of antioxidants within the body while producing reactive nitrogen species (RNS). ROS generated by oxidative stress disrupts cell signaling, DNA damage, lipids, and proteins, thereby resulting in inflammation and apoptosis. Mitochondria is the primary source of ROS production within cells. Increased ROS production reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction within the arteries and contributes to the development of hypertension. ROS production has also been linked to the development of atherosclerotic plaque. Antioxidants can decrease oxidative stress in the body; however, various therapeutic drugs have been designed to treat oxidative stress damage due to CVD. The present review provides a detailed narrative of the oxidative stress and ROS generation with a primary focus on the oxidative stress biomarker and its association with CVD. We have also discussed the complex relationship between inflammation and endothelial dysfunction in CVD as well as oxidative stress-induced obesity in CVD. Finally, we discussed the role of antioxidants in reducing oxidative stress in CVD.

DNA Fingerprint Technology: Its Application in Detecting Pancreatic Cancer.

Pancreatic cancer (PC) is one of the most lethal forms of cancers, ranking as the third highest cause of malignancies and fatalities. Approximately 88% of patients diagnosed with PC are older than 55 yr. Due to PC's vague symptoms, patients typically visit their doctor only when they experience symptoms of extreme pain and/or after their bile ducts have blocked. This produces symptoms including darkly colored urine, jaundice, and light-colored stools. At this point in the progression of the disease, the tumor has already metastasized. Early detection of PC is critical and justifies the need for innovative techniques to efficiently aid in this process. Current research involves screening different aspects of the disease, imaging techniques, and evaluating blood, urine, cell, and saliva biomarkers. We propose that forensic DNA fingerprinting can be used to establish the role of genetics in PC, and we describe disease inheritance patterns so that relatives can understand the likelihood of developing this lethal malignancy.

Nanoparticles in Pancreatic Cancer Imaging and Therapy.

Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in both men and women. Because most PC patients are initially diagnosed at an advanced stage of disease, effective diagnostic tests for earlier diagnosis of PC are needed. Several studies have investigated the utility of nanoparticle for both diagnosis and therapy of PC. This review discusses the various engineered nanoparticles currently in use for imaging and therapy. Although nanoparticles have shown considerable clinical promise, complete translation of nanoparticle-based molecular imaging and oncotherapeutic agents has been the challenge.

Compound Heterozygosity of ß-Thalassemia and the Sickle Cell Hemoglobin in Various Populations of Chhattisgarh State, India.

Hemoglobinopathies evolved as a protective mechanism against malaria, which exhibit selective advantage in the heterozygous state. However, in a homozygous recessive condition, it poses a serious socioeconomic burden. Sickle cell anemia is an autosomal recessive hemoglobinopathy associated with erythrocytes sickling, vaso-occlusive crisis (VOC), as well as multi-organ failure and death. The coinheritance of other hemoglobinopathies is known to substantially modulate the clinical manifestation of sickle cell anemia. In the present study, we aimed to analyze the coinheritance of ß-thalassemia (ß-thal) in Hb S (HBB: c.20A>T) patients. The study includes 918 sickle cell anemia patients from 10 ethnic populations of Chhattisgarh State, India. Complete blood counts (CBCs) and hemoglobin (Hb) high performance liquid chromatography (HPLC) fractionation data were collected from patient record books. We observed Hb S-ß-thal in all the analyzed populations. Interestingly, high frequencies of Hb S-ß-thal have been observed in Satnami (53.8%), Rawat (47.1%), Gond (35.1%) and Panika (30.6%) populations. Inter-population comparison of hematological parameters [Hb F (p < 0.001), Hb A2 (p < 0.001), Hb (p = 0.03) and red blood cell distribution width (RDW) (p < 0.001)] revealed significant differences. We also observed that mean Hb F levels were significantly higher in Hb S compared to Hb S-ß-thal patients in the respective populations. Our study highlights the higher prevalence of ß-thal as well as the compound heterozygosity for Hb S and ß-thal in various populations of Chhattisgarh State, India.

Pain Management Issues as Part of the Comprehensive Care of Patients with Sickle Cell Disease.

BACKGROUND: Vaso-occlusive pain crisis is one of the primary complications of sickle cell disease (SCD) and is responsible for the majority of hospital visits in patients with SCD. Stints of severe pain can last for hours to days and are difficult to treat and manage, often resulting in drastically reduced quality of life. PURPOSE: Our purpose is to provide an overview of pain management issues in SCD populations. METHODS: We explored literature using PubMed and Embase for the etiology and management of pain in SCD. Databases were searched employing the following terms: sickle cell, pain pathways, pain perception, pharmacological therapies, psychological therapies, physical therapies and genetics. RESULTS: Pain in SCD can vary from acute to chronic (persistent) or mixed and understanding of the underlying mechanisms is important for proper pain management. Currently, there are many means of managing pain in children with SCD, which involve pharmacological and non-pharmacological approaches. A combination of psychotherapy and pain medications can be used for treatment of pain and other psychosocial co-morbidities in complex persistent pain. CONCLUSIONS: Providing more appropriate medication and optimal dosage based on individual's genomic variations is the future of medicine, and this will allow the physicians to hone in on optimal pain management in patients with SCD.

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population / Polimorfismo de nucleotídeo único do gene IRF6 rs2235375 está associado com à fenda palatina isolada não sindrômica, mas não com fenda labial com ou sem fenda palatina em população do sul da Índia

Abstract Introduction Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. Objective We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. Methods 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. Results There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p = 0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p = 0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p = 0.005). Conclusion These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Resumo Introdução Fatores de transcrição constituem uma família de proteínas muito diversa envolvida na ativação ou repressão da transcrição de um gene, em um determinado momento. Vários estudos usando modelos animais demonstraram o papel dos genes do fator de transcrição no desenvolvimento craniofacial. Objetivo Nosso objetivo foi investigar a associação do polimorfismo IRF6 intron-6 na fenda labial não sindrômica com ou sem fenda palatina em uma população do sul da Índia. Método Um total de 173 pacientes com fenda labial não sindrômica com ou sem fenda palatina e 176 controles sem fendas foram genotipados para a variante IRF6 rs2235375 por amplificação alelo-específica utilizando o sistema KASPar de genotipagem de polimorfismo de nucleotídeo único. A associação entre o polimorfismo de nucleotídeo único Fator 6 Regulatório do Interferon (IRF6) intron-6 dbSNP208032210:g.G>C (rs2235375) e o risco de fenda labial não sindrômica com ou sem fenda palatina foi investigado pelo teste qui-quadrado. Resultados Houve diferenças significativas nas frequências de genótipos ou alelos do rs2235375 SNP entre controles e casos com fenda labial não sindrômica com ou sem fenda palatina. A variante IRF6 rs2235375 foi significativamente associada ao aumento do risco de fenda labial não sindrômica com ou sem fenda palatina em modelos codominantes, dominantes (OR: 1,19; IC 95%: 1,03-2,51; p = 0,034) e alélicos (OR: 1,40; IC 95%: 1,04-1,90; p = 0,028). Quando a análise do subgrupo foi realizada, um risco significativamente aumentado foi observado no grupo Fenda Palatina Isolada (OR dominante: 4,33; IC 95%: 1,44-12,97; p = 0,005). Conclusões Esses resultados sugerem que o polimorfismo de nucleotídeo único IRF6 rs2235375 desempenha um papel importante na patogênese e no risco de desenvolvimento de fenda labial não sindrômica com ou sem fenda palatina.

Relationship between matrilin-1 gene polymorphisms and mandibular retrognathism.

INTRODUCTION: Mandibular retrognathism is a type of malocclusion that refers to an abnormal posterior position of the mandible as a result of a developmental abnormality. From the literature, it is evident that the mandibular growth pattern is determined by the intramembranous ossification of the mandibular body and endochondral ossification of the condyle. Matrilin-1 is a cartilage extracellular matrix protein, and matrilin-1 gene (MATN1) polymorphisms have been found to be involved in dental malocclusions of humans. In this study, we aimed to examine the association between MATN1 polymorphisms and the risk of mandibular retrognathism, in a case-control study with a South Indian population. METHODS: Eighty-one patients with mandibular retrognathism (SNB, <78°) and 71 controls having an orthognathic mandible (SNB, 80° ± 2°) were recruited. In both the patient and control groups, subjects with an orthognathic maxilla (SNA, 82° ± 2°) were included. Three single nucleotide polymorphisms of the MATN1 gene (rs1149048, rs1149042, and rs1065755) were genotyped using polymerase chain reaction-restriction fragment length polymorphism. The statistical association analysis was performed using the chi-square test. Pair-wise linkage disequilibrium was computed, and haplotypes were compared between subjects and controls. Nonparametric tests were used to compare cephalometric measurements between groups. RESULTS: No polymorphic site deviated from Hardy-Weinberg equilibrium in the controls. The rs1149042 genotypes and alleles were found to be associated with reduced risk of mandibular retrognathism. Furthermore, rs1149042 genotypes were associated with mandibular measurements (SNB and ANB). There was no strong and consistent linkage disequilibrium linkage disequilibrium across two different single nucleotide polymorphisms and haplotypes were not associated with mandibular retrognathism. CONCLUSIONS: The results of our study suggest an association between the MATN1 gene polymorphisms and mandibular retrognathism.

IRF6 rs2235375 single nucleotide polymorphism is associated with isolated non-syndromic cleft palate but not with cleft lip with or without palate in South Indian population.

INTRODUCTION: Transcription factors are very diverse family of proteins involved in activating or repressing the transcription of a gene at a given time. Several studies using animal models demonstrated the role of transcription factor genes in craniofacial development. OBJECTIVE: We aimed to investigate the association of IRF6 intron-6 polymorphism in the non-syndromic cleft lip with or without palate in a South Indian population. METHODS: 173 unrelated nonsyndromic cleft lip with or without cleft palate patients and 176 controls without clefts patients were genotyped for IRF6 rs2235375 variant by allele-specific amplification using the KASPar single nucleotide polymorphism genotyping system. The association between interferon regulatory factor-6 gene intron-6 dbSNP208032210:g.G>C (rs2235375) single nucleotide polymorphism and non-syndromic cleft lip with or without palate risk was investigated by chi-square test. RESULTS: There were significant differences in genotype or allele frequencies of rs2235375 single nucleotide polymorphism between controls and cases with non-syndromic cleft lip with or without palate. IRF6 rs2235375 variant was significantly associated with increased risk of non-syndromic cleft lip with or without palate in co-dominant, dominant (OR: 1.19; 95% CI 1.03-2.51; p=0.034) and allelic models (OR: 1.40; 95% CI 1.04-1.90; p=0.028). When subset analysis was applied significantly increased risk was observed in cleft palate only group (OR dominant: 4.33; 95% CI 1.44-12.97; p=0.005). CONCLUSION: These results suggest that IRF6 rs2235375 SNP play a major role in the pathogenesis and risk of developing non-syndromic cleft lip with or without palate.

Retrospection on the Role of Soluble Guanylate Cyclase in Parkinson's Disease.

Soluble guanylate cyclase (sGC) is an important transducing enzyme of cyclic guanosine monophosphate (cGMP) signaling pathway in striatum which has been considered as a potential target for the treatment of Parkinson's disease. Etiology of Parkinson's disease is multifactorial, finally resulting in abnormal proteinopathies causing degeneration of nigrostriatal pathways. Understanding the pathological basis of Parkinson's disease at molecular level is still an achievable target for the researchers and clinical practitioners. sGCs may be one of the causative factors resulting in Parkinson's disease due to glutamate toxicity or other event. This review presents the literature from articles of past five decades nearly as still this enzyme protein and its role in Parkinson's disease is not that clearly understood or presented till date. Recent interventions of this protein inhibition in the treatment of Parkinson's disease preclinically gave a chance to review the literature about this enzyme and its correlation with factors causing Parkinson's disease. We explored literature using PubMed and EMBASE for the role of sGC in Parkinson's disease. Databases were searched using the following terms: Parkinson's disease, neurotoxins, guanylate cyclase, sGC-cGMP pathway, and neurodegeneration. This review listed out the factors that have probability for stimulating sGC which already have been listed as a neurotoxins causing Parkinson's disease.

Transmission analysis of TGFB1 gene polymorphisms in non-syndromic cleft lip with or without cleft palate.

OBJECTIVES: Transforming growth factor beta1 (TGF-ß1) plays a significant role in craniofacial development. Previous linkage studies reported that the TGF-ß1-locus at 19q13.1 harbour predisposing genes for non-syndromic oral clefts. In the present study case parents triads were evaluated to find the transmission effects of genetic variants in TGF- ß1 towards non-syndromic cleft lip or palate (NSCL/P). METHODS: Using allelic discrimination method148 families (case-parent triads) were assessed for single nucleotide polymorphisms (SNPs) in TGF-ß1 gene. The SNPs were checked for mendelian errors and Hardy-Weinberg equilibrium (HWE). Transmission disequilibrium test and haplotype frequencies were estimated. RESULTS: The TGF-ß1 SNPs showed very low minor allele frequencies (MAFs) and observed heterozygosity (Hobs). The transmission disequilibrium test (TDT) and parent-of-origin likelihood ratio tests (PO-LRT) were not significant for any of the SNPs tested. Strong linkage disequilibrium (r2 = 0.722) was found between rs1800469 and rs1800470 SNPs. Haplotype analysis ignoring parent of origin showed strong evidence of excess transmission but it is not significant (p-value = 0.293). CONCLUSION: Transmission of minor alleles were not observed from either parent indicating that the TGF-ß1 gene polymorphisms by themselves do not confer risk for non-syndromic oral clefts but, rather, modify the stability and the activation process of TGF-ß1. As the number of families included in the study are less, results must be considered still preliminary and require replication using more families.

Assessment of renal function in Indian patients with sickle cell disease.

Sickle cell disease (SCD) and its variants are genetic disorders resulting from the presence of a mutated form of hemoglobin. Renal disease is one of the most frequent complications, and kidney damage starts very early and progresses throughout life causing severe complications. The present study is aimed to analyze creatinine-based estimated glomerular filtration rate (eGFR) in 616 SCD patients (507 HbSS and 109 HbSB+), receiving medical care at outpatient wing of Sickle Cell Institute, Chhattisgarh. Glomerular filtration rate (GFR) estimated using the Modification of Diet in Renal Disease (MDRD), Cockcroft-Gault, chronic kidney disease epidemiology collaboration (CKD-EPI) (<17 years analyzed with Schwartz), and SCD specific Jamaica Sickle Cell Cohort Study (JSCCS)-GFR equations were compared. Further, eGFR calculated using the CKD-EPI and Schwartz equations was used to define various stages of kidney function and compared with clinical and hematological variables. The mean age of patients was 15.8 years. Comparison of eGFR using various formulas revealed that MDRD and JSCCS formulas overestimated the GFR. Among SCD patients, prevalence of glomerular hyperfiltration (GHF) is high followed by renal insufficiency (RI) and renal failure (RF). However, no differences were found in hematological profiling among different functional stages of kidney. Age and body surface area are significantly more in SCD individuals with normal kidney function and GHF. Participants with RF showed a higher level of blood urea and fetal hemoglobin. In summary, this is the first study to analyze different functional stages of kidney among SCD patients of India. Our study revealed that the GHF and RI are the important indicators of kidney damage.

Aldosterone synthase gene is not a major susceptibility gene for progression of chronic kidney disease in patients with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common heritable kidney disease and is characterized by bilateral renal cysts. Hypertension is a frequent cause of chronic kidney disease (CKD) and mortality in patients with ADPKD. The aldosterone synthase gene polymorphisms of the renin-angiotensin-aldosterone system have been extensively studied as hypertension candidate genes. The present study is aimed to investigate the potential modifier effect of CYP11B2 gene on the progression of CKD in ADPKD. One hundred and two ADPKD patients and 106 healthy controls were recruited based on Ravine inclusion and exclusion criteria. The three tag-SNPs within CYP11B2 gene (rs3802230, rs4543, and rs4544) were genotyped using FRET-based KASPar method. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Mantel- Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. Of the three tag-SNPs genotyped, rs4544 polymorphism was monomorphic and rs3802230 deviated Hardy-Weinberg equilibrium. The CYP11B2 tag-SNPs did not show significant association with ADPKD or CKD. Further, these polymorphisms did not exhibit confounding effect on the relationship between CKD progression and hypertension. Our results suggest that aldosterone synthase gene is not a major susceptibility gene for progression of CKD in South Indian ADPKD patients.

Attitudes and beliefs among high- and low-risk population groups towards ß-thalassemia prevention: a cross-sectional descriptive study from India.

ß-thalassemia is an autosomal recessive blood disorder caused by gene mutations that affect all aspects of ß-globin production. In majority of Asian countries including India, the frequency of ß-thalassemia is closely intertwined with social, cultural, and religious issues of the respective country. Several national level screening programs imparted education regarding ß-thalassemia, but follow-up evaluation revealed that education was not effective. It has been hypothesized that the beliefs and attitudes, carrier screening, and education among "high risk communities" will have far-reaching implications towards ß-thalassemia prevention in the country. The present study is aimed to investigate attitudes, intention, and behavior of ß-thalassemia high- and low-risk ethnic groups towards carrier screening and education. A structured questionnaire on knowledge, attitude, and practice regarding ß-thalassemia was administered on 926 individuals belong to Arora, a high-risk ethnic group for ß-thalassemia (347 rural (AR) and 202 urban (AU)) and 377 cosmopolitan commoners (CC) aged above 18 years of both sexes. To understand the relationship between various questions, Pearson's correlation test and factor analysis was performed. The responses were further categorized into the theory of planned behavior (TPB) constructs with the measures of the main constructs reported as a mean. Various dimensions of knowledge, attitude, and practice reveal that the urban groups (AU and CC) are better aware of the disease "ß-thalassemia" than the rural group (AR) who witness suffering at close quarters. The AR group is more positive for preventive measures than the urban groups. Significant correlations and factor analysis show "intentions" for premarital and prenatal screening highly loaded as outcome behaviors. The Ajzen's "Theory of planned behavior" support that the "intention" and "perceived behavior control" are better predictors of "outcome behavior" compared to "attitude" and "subjective norm." As this study is cross-sectional and descriptive in nature, the constructs of the theory should be considered as perceptions. However, we believe the patterns observed are indicative of "predicting behavior" that has far-reaching implications on health planners and administrators in designing ß-thalassemia screening and prevention program.

Influence of angiotensin converting enzyme (ACE) gene rs4362 polymorphism on the progression of kidney failure in patients with autosomal dominant polycystic kidney disease (ADPKD).

BACKGROUND & OBJECTIVES: Autosomal dominant polycystic kidney disease (ADPKD) is an inherited systemic disorder, characterized by the fluid filled cysts in the kidneys leading to end stage renal failure in later years of life. Hypertension is one of the major factors independently contributing to the chronic kidney disease (CKD) progression. The renin-angiotensin aldosterone system (RAAS) genes have been extensively studied as hypertension candidate genes. The aim of the present study was to investigate the role of angiotensin converting enzyme tagging - single nucleotide polymorphisms (ACE tag-SNPs) in progression of CKD in patients with ADPKD. m0 ethods: In the present study six ACE tagSNPs (angiotensin converting enzyme tag single nucleotide polymorphisms) and insertion/deletion (I/D) in 102 ADPKD patients and 106 control subjects were investigated. The tagSNPs were genotyped using FRET-based KASPar method and ACE ID by polymerase chain reaction (PCR) and electrophoresis. Genotypes and haplotypes were compared between ADPKD patients and controls. Univariate and multivariate logistic regression analyses were performed to assess the effect of genotypes and hypertension on CKD advancement. Mantel-Haenszel (M-H) stratified analysis was performed to study the relationship between different CKD stages and hypertension and their interaction. RESULTS: All loci were polymorphic and except rs4293 SNP the remaining loci followed Hardy-Weinberg equilibrium. Distribution of ACE genotypes and haplotypes in controls and ADPKD patients was not significant. A significant linkage disequilibrium (LD) was observed between SNPs forming two LD blocks. The univariate analysis revealed that the age, hypertension, family history of diabetes and ACE rs4362 contributed to the advancement of CKD. INTERPRETATION & CONCLUSIONS: The results suggest that the ACE genotypes are effect modifiers of the relationship between hypertension and CKD advancement among the ADPKD patients.

Role of myosin 1H gene polymorphisms in mandibular retrognathism.

INTRODUCTION: Mandibular retrognathism may be the result of a developmental abnormality or the unfavorable positional relationship of developing jaws. Several lines of evidence suggest that muscles are known to have extensive mutual effects on bones. Studies with immunohistochemical staining and gene expression have shown unique combinations of myosin heavy chain isoforms in the masseter muscles. In this study, we aimed to evaluate MYO1H gene polymorphisms and haplotypes as risk factors for mandibular retrognathism. METHODS: Twenty-five subjects with mandibular retrognathism and 25 control subjects of both sexes having an orthognathic maxilla (SNA, 82° ± 2°) between the ages of 12 and 30 years of age were selected for this study. Based on the cephalometric values, subjects with SNB angles smaller than 78° were considered to have mandibular retrognathism. Orthognathic subjects (SNB, 80°) without jaw deformations were used as the comparison group. Three polymorphisms of MYO1H gene (rs10850110, rs11611277, and rs3825393) were genotyped using polymerase chain reaction and restriction fragment length polymorphism. Associations were tested with the Pearson chi-square test and haplotype analyses. RESULTS: The single nucleotide polymorphism rs3825393 showed a statistically significant association with mandibular retrognathism. The cephalometric variables SNB and ANB angles showed significant differences among the various genotypes of rs3825393. Linkage disequilibrium was not strong and significant between the single nucleotide polymorphisms; hence, the haplotypes of the MYO1H gene are not associated with mandibular retrognathism. CONCLUSIONS: These results suggest that the rs3825393 polymorphism of the MYO1H gene is associated with an increased risk for mandibular retrognathism. The relatively small sample size used in the study resulted in modest statistical power. A parallel investigation on another population with larger samples to increase the power could further clarify the role of the MYO1H gene in causing mandibular retrognathism.

Renin gene rs1464816 polymorphism contributes to chronic kidney disease progression in ADPKD.

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is a monogenic disorder and is a common genetic cause of chronic renal failure in children and adults. The enzyme renin plays a key role in the RAAS cascade and an important role in the development of hypertension and progression of renal disease in ADPKD. The present study is aimed to investigate the potential modifier effect of REN gene polymorphisms on the progression of chronic kidney disease (CKD) in ADPKD. METHODS: We analyzed 102 ADPKD patients and 106 healthy controls from the same geographic area. FRET-based KASPar single-nucleotide polymorphism (SNP) genotyping assays for REN gene tag-SNPs (rs2887284, rs2368564, rs1464816, rs7521667, rs10900555, rs6693954, rs6676670 and rs11571078) were performed. Cochran-Armitage trend test was used to assess the potential associations between these polymorphisms and CKD stages. Haplotype frequencies and LD measures were estimated by using the software Haploview. Mantel-Haenszel stratified analysis was used to explore confounding and interaction effects of these polymorphisms. RESULTS: Of the eight tag-SNPs genotyped, the rs10900555 polymorphism deviated from the Hardy-Weinberg equilibrium in controls. The presence of ADPKD in general was not significantly associated with the REN tag-SNPs included in this study. Linkage disequilibrium analysis yielded three haplotype blocks and the haplotypes of the respective blocks are not statistically different between ADPKD and controls. In multivariate analysis, the rs1464816 TG genotype showed a significant association with the advancement of CKD in ADPKD (OR = 4.80; 95 % CI = 1.30-17.82; p = 0.019). CONCLUSIONS: The present study provides evidence that the rs1464816 polymorphism in REN is associated with CKD progression in ADPKD.

Endothelin 1 gene is not a major modifier of chronic kidney disease advancement among the autosomal dominant polycystic kidney disease patients.

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the presence of numerous cysts in the kidney and manifest with various renal and extra-renal complications leading to ESRD. Endothelin may contribute to various renal and extra-renal manifestations pointing to genetic and environmental modifying factors that alter the risk of developing chronic kidney disease (CKD) in ADPKD. In the present study we investigated six genes coding for endothelin 1 ( EDN1 ) tagging-single nucleotide polymorphisms (tag-SNPs) to unravel the EDN1 gene modifier effect for renal disease progression in ADPKD. Materials and Methods: The tag-SNPs were genotyped using FRET-based KASPar method in 108 ADPKD patients and 119 healthy subjects. Cochran-Armitage trend test was used to determine the association between ADPKD and EDN1 tag-SNPs. Multivariate logistic regression analysis was performed to assess the effect of tag-SNPs on CKD progression. The relationship between different CKD stages and hypertension and their interaction Mantel-Haenszel stratified analysis was performed. Results: All loci are polymorphic and followed Hardy-Weinberg equilibrium. Distribution of EDN1 genotypes and haplotypes in control and ADPKD is not statistically significant. Five SNPs covering 3.4 kb forming single LD block, but the LD was not strong between SNPs. The EDN1 genotypes are not contributing to the CKD advancement among the ADPKD patients. Conclusion: These results suggest that the EDN1 gene is not a major modifier of CKD advancement among ADPKD patients.