Association between opioid and dopamine receptor gene polymorphisms OPRM1 rs1799971, DAT VNTR 9-10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 and alcohol dependence: an ethnicity oriented meta-analysis.

OBJECTIVE: We carried out a meta-analysis of four opioid and dopamine candidate gene polymorphisms having conflicting results in prior literature, namely OPRM1 rs1799971, DAT VNTR 9-10 repeat, DRD1 rs4532 and DRD2 rs1799732, to clarify their association with alcohol dependence and further stratified results by ethnicity to analyze possible ethnicity-mediated effects. METHODS: Inclusion criteria: case-control studies assessing the association between OPRM1 rs1799971, DAT VNTR 9/10 repeat allele, DRD1 rs4532 and DRD2 rs1799732 with alcohol dependence, with sufficient data available to calculate the odds ratio (OR) within a 95% confidence interval. Exclusion criteria: studies of quantitative measures of alcohol consumption, response to medications or analyses of other markers in the candidate genes, studies without controls, animal studies and lack of genotyping data. Information sources were PubMed, Google Scholar and ScienceDirect databases, all of which were searched for articles published till 2021. Heterogeneity between studies and publication bias, subgroup analyses and sensitivity analyses were carried out. RESULTS: A total of 41 published studies were included in the current meta-analysis. For the OPRM1 gene, there was a statistically significant association in the Asian population with a pooled OR of 1.707 (95% CI, 1.32-2.20 P < 0.0001) and 1.618 (95% CI, 1.16-2.26 P = 0.005) in the additive and dominant genetic models. For DAT VNTR 9/10 repeat, a statistically significant association of the risk vs. common allele was observed in AD with a pooled OR of 1.104 (95% CI, 1.00-1.21 P = 0.046) in the allele model and the additive genetic model in the Caucasian population with pooled OR of 1.152 (95% CI, 1.01-1.31 P = 0.034). CONCLUSION: Results indicate that some of the effects may be ethnicity-specific. OTHER: The meta-analysis has been registered in the CRD PROSPERO (CRD42023411576).

Impact of Serotonin Pathway Gene Polymorphisms and Serotonin Levels in Suicidal Behavior.

OBJECTIVE: Suicide is a significant public health issue and a major cause of death in all ages worldwide. Previous studies have shown the involvement of genetics in suicidal behaviour. This study aimed to assess the role of the genetic variants of the serotonin transporter genes (5HTTLPR, SLC6A4 intron 2) and receptor gene (5HTR2AT102C) in individuals who died of suicide. The study compares the serum levels of serotonin between the cases and controls. METHODS: We conducted a case control study with 120 cases and 126 controls. Socio-economic details of the subjects were collected using a semi-structured proforma and psychological autopsy was used to collect details of medical and other clinical conditions. Blood was drawn after taking informed consent and serum levels of serotonin were estimated by ELISA. Genotyping was performed using appropriate primers followed by polymerase chain reaction (PCR) and a restriction fragment length polymorphism (RFLP). RESULTS: Mean age was 32.59 ± 12.58 for cases and 33.64 ± 9.78 for controls. The risk associated LL genotype of 5HTTLPR was higher among cases. The heterozygous 12/10 genotype of SLC6A4 intron 2 polymorphism was increased among controls. Serum levels of serotonin were lower among cases. Variant genotypes of all the 3 polymorphisms showed significant interaction (OR= 39.26) indicating that this model may increase suicidal tendency. CONCLUSION: The findings of this study suggest that low serum levels of serotonin and two variants of the serotonin gene may influence suicide behaviour in a south Indian population.

Differential urinary microRNA expression analysis of miR-1, miR-215, miR-335, let-7a in childhood nephrotic syndrome.

BACKGROUND: Recently, urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases and they exhibit great potential as noninvasive biomarkers for the diagnosis of various diseases. The present study was aimed to evaluate the expression status of selected miRNAs (miR-1, miR-215-5p, miR-335-5p and let-7a-5p) in urine samples from children with NS [steroid sensitive (SSNS)] and [steroid resistant (SRNS)] along with healthy control group. METHODS: MicroRNA isolation was carried out in urine samples collected from SSNS (100 nos), SRNS (100 nos), and healthy controls (50 nos) using MiRNeasy Mini Kit, followed by cDNA conversion for all the four selected miRNAs using Taqman advanced miRNA cDNA synthesis kit and their expression was quantified by Taqman Advanced miRNA assay kits using Real Time PCR Machine and Rotogen-Q in SSNS and SRNS patients and healthy control subjects. RESULTS: Quantification of all the four miRNAs (miR-1, mir-215, miR-335, let-7a) were found to be upregulated in both SSNS and SRNS as compared to control group. Further, the comparison of microRNAs within the case groups revealed significant downregulation of three microRNAs-miR-1, miR-215, miR- 335 and upregulation of let-7a in SRNS group as compared to SSNS. The t-test performed for all the four miRNAs was found to be statistically significant. CONCLUSIONS: The aberrant expression of all the four microRNAs in both SSNS and SRNS as compared to healthy subjects may serve as novel biomarkers to distinguish between NS and healthy controls. The differential expression of microRNA let-7a is useful to discriminate SSNS and SRNS.

Role of serotonin transporter and receptor gene polymorphisms in treatment response to selective serotonin reuptake inhibitors in major depressive disorder.

OBJECTIVE: Significant challenges in the management of major depressive disorder include the lag period from treatment initiation to an evident response, low response rates and unpredictable disparities in outcome between patients. As a large part of these has been linked to genetic mechanisms, we tried to establish a relationship between genes associated with serotonin neurotransmission and outcome to selective serotonin reuptake inhibitor (SSRI) treatment. METHODS: One hundred and twenty-five patients with moderate to severe depression [at least 15 on the Hamilton Depression (HAM-D) Rating Scale] being started on SSRI were recruited. Those with a reduction of at least 50% from baseline or an absolute score of 7 or less after 8 weeks of treatment were considered as responders. The serotonin transporter linked polymorphic region 5HTTLPR, serotonin transporter intron 2 (STin2) polymorphism and the 5-HT receptor 1A rs6295 polymorphisms were studied in association with outcome. RESULTS: The l/l genotype of the 5HTTLPR was associated with greater likelihood of response (OR: 4.65, CI: 1.74-12.38, p = 0.003). Patients with the 12/12 repeat variant of the STin2 VNTR polymorphism showed a greater reduction in HAM-D score, compared to patients with the 10/10 genotype (OR: 0.12, CI: 0.03-0.44, p = 0.001). We found no association of the 5HTR1Ars6295 polymorphism with response. CONCLUSIONS: The 5HTTLPR polymorphism and the SLC6A4 intron 2 polymorphism were associated with treatment response, with the l/l genotype and 12-copy allele showing a tendency towards better outcomes, respectively.

MicroRNAs in childhood nephrotic syndrome.

The discovery of microRNAs (miRNAs) has opened up new avenues of research to understand the molecular basis of a number of diseases. Because of their conservative feature in evolution and important role in the physiological function, microRNAs could be treated as predictors for disease classification and clinical process based on the specific expression. The identification of novel miRNAs and their target genes can be considered as potential targets for novel drugs. Furthermore, currently, the circulatory and urinary exosomal miRNAs are gaining increasing attention as their expression profiles are often associated with specific diseases, and they exhibit great potential as noninvasive or minimally invasive biomarkers for the diagnosis of various diseases. The remarkable stability of these extracellular miRNAs circulating in the blood or excreted in the urine underscored their key importance as biomarkers of certain diseases. There is voluminous literature concerning the role of microRNAs in other diseases, such as cardiovascular diseases, diabetic nephropathy, and so forth. However, little is known about their diagnostic ability for the pediatric nephrotic syndrome (NS). The present review article highlights the recent advances in the role of miRNAs in the pathogenesis and molecular basis of NS with an aim to bring new insights into further research applications for the development of new therapeutic agents for NS.

Association of Serum Biomarker Levels and BDNF Gene Polymorphism with Response to Selective Serotonin Reuptake Inhibitors in Indian Patients with Major Depressive Disorder.

INTRODUCTION: Depression is a major public health problem. Response to selective serotonin reuptake inhibitor (SSRI) treatment varies considerably between patients. In the context of polygenic diseases like depression, measurement of a panel of biomarkers involved in the pathophysiology of depression might help predict outcome to treatment with SSRIs. OBJECTIVE: The objective was to establish the relationship between serum biomarker levels and the brain-derived neurotrophic factor (BDNF) val66met polymorphism and response to SSRIs in patients with major depressive disorder. METHODS: 50 patients with moderate to severe depression were recruited from the Department of Psychiatry, Sri Ra-machandra Institute of Higher Education and Research. Blood samples were collected, and Hamilton Depression Rating Scale scoring was done at baseline and after 8 weeks of treatment with SSRIs. Baseline and post-treatment levels of high-sensitivity C-reactive protein (hsCRP), BDNF and neuregulin 1ß1 (NRG1ß1) were analysed using commercially available ELISA kits. Genotyping of the BDNF Val66Met polymorphism was performed using a PCR-RFLP method. RESULTS: Following treatment, there was a significant decrease in the mean hsCRP and NRG1ß1 levels and a significant increase in the mean BDNF level. Responders had significantly lower baseline hsCRP and higher baseline BDNF levels when compared to non-responders. Response rates were significantly higher in the Val/Val group when compared to the Val/Met group. CONCLUSIONS: Baseline serum levels of hsCRP and BDNF predicted response to SSRIs in major depressive disorder, and Val/Val patients responded better when compared to patients carrying the Met allele.

Differentially expressed miR-20, miR-21, miR-100, miR-125a and miR-146a as a potential biomarker for prostate cancer.

Prostate cancer is the leading cause of death among men worldwide. Deregulation of microRNAs has been reported in many cancers. Expression of microRNAs miR-20a-5p, miR-21-5p, miR-100-5p, miR-125a-5p and miR-146a-5p in tissue blocks of histologically confirmed prostate cancer patients compared with BPH patients, to identify potential microRNA biomarker for prostate cancer. MicroRNA was isolated and expression was quantified by qRT-PCR using Taqman Advanced microRNA assay kits. The interactions between the microRNA:target mRNA were predicted by using bioinformatics tools such as miRwalk and miRTargetlink. The experimentally validated targets were analysed using gprofiler to identify their molecular function, biological process and related pathways. The expression analysis revealed that miR-21 and miR-100 were significantly down-regulated whereas miR-125a was up-regulated in prostate cancer patients. Comparative analysis of the expression levels with tumor grading reveal that miR-100 was significantly down-regulated (p < 0.05) in high grade tumor, indicating that miR-100 associated with prostate cancer. ROC analysis revealed that combined analysis of down-regulated miRNAs (miR-21 and miR-100) shown AUC of 0.72 (95% CI 0.65-0.79). The combined analysis of all five miRNAs showed AUC of 0.87 (95% CI 0.81-0.92). The targets prediction analysis revealed several validated targets including BCL2, ROCK1, EGFR, PTEN, MTOR, NAIF1 and VEGFA. Our results provide evidence that combined analysis of all the five miRNAs as a panel can significantly improve the prediction level of the presence of prostate cancer and may be used as a potential diagnostic biomarker.

Differential expression of microRNAs let-7a, miR-125b, miR-100, and miR-21 and interaction with NF-kB pathway genes in periodontitis pathogenesis.

Periodontitis is a chronic inflammatory disease which is caused by destruction of the tissues that surrounds and supports the tooth. Deregulation of microRNAs has been reported to cause several inflammatory diseases such as autoimmune disease, chronic periodontitis, and cancer. In the present study, we have investigated the expression pattern of microRNAs let-7a, miR-125b, miR-100, miR-21, and RNA-binding protein LIN-28A among healthy individuals and chronic periodontitis patients. Total RNA was isolated from gingival tissue samples collected from 100 healthy individuals and 100 chronic periodontitis patients. The expression of microRNAs and LIN-28 was performed by qPCR. Target prediction for the microRNAs was done using miRWalk and miRTarbase online databases and the experimentally validated targets were analyzed for their molecular function, biological processes, and related pathways using gProfiler software. The expression analysis revealed that let-7a and miR-21 were upregulated, whereas, miR-100, miR-125b, and LIN-28 were down regulated. The age dependent expression analysis revealed that the expression levels of all the microRNAs and LIN-28 were found to increase with age (more than 50 years), thereby suggesting an increased risk to chronic periodontitis. Among the various targets predicted using miRWalk and miRTarbase databases, NFKB was found to be a common target among all the four microRNAs. gProfiler revealed several functions such as NF-ĸB signaling pathway, cytokine-cytokine receptor interaction, osteoclast differentiation, etc., all of which specific to inflammation and periodontitis.

Report of novel genetic variation in NPHS2 gene associated with idiopathic nephrotic syndrome in South Indian children.

BACKGROUND: Steroid-resistant nephrotic syndrome (SRNS) is found in 10-20 % of children with idiopathic nephrotic syndrome (INS). In SRNS patients, common histopathological subtypes are Focal segmental glomerulosclerosis (FSGS) (53 %) and minimal change disease (MCD) (27 %). Familial forms of FSGS constitute podocyte diseases with varying severity and age of onset. Podocin gene (NPHS2) mutations cause childhood-onset steroid-resistant FSGS and MCD to adult-onset FSGS. In view of genetic variations and susceptibility to the disease, the present investigation was undertaken to study the pattern of genetic mutation in children from South India. METHODS: Mutation analysis was carried out by direct sequencing of the entire NPHS2 gene (eight exons) using specific primers in 200 INS (100 SRNS and 100 steroid sensitive) children and 100 healthy controls. The allele and genotype frequencies of NPHS2 gene were calculated for both cases and controls as per Hardy-Weinberg equilibrium. RESULTS: Among the SRNS patients, 18 % revealed both heterozygous and homozygous mutations. Out of 12 mutations, 8 were homozygous and 4 were heterozygous. Interestingly, we found two novel SNPs in exon 4 of NPHS2 gene, which are documented and submitted to dbsnp database (Ref rs12401711 and rs12401708). CONCLUSION: Mutational analysis of NPHS2 would be advisable at the start of treatment. The genetic variations detected in the study would serve as the important molecular marker in treating the children's at early stage, which also enables to detect carriers, prenatal diagnosis and provide genetic counseling to couples at risk.

Genetic variation in matrix metalloproteinase MMP2 and MMP9 as a risk factor for idiopathic recurrent spontaneous abortions in an Indian population.

PURPOSE: Matrix metalloproteinases, MMP2 and MMP9, are found to have an important role during ovulation and pregnancy because of their capacity to degrade components of the extracellular matrix (ECM) thereby facilitating cell migration and angiogenesis. In this respect, the aim of the present study was to evaluate the association of the promoter polymorphisms -1306 C > T and -1562 C/T in MMP2 and MMP9 respectively with couples diagnosed with idiopathic recurrent spontaneous abortions (IRSA). The expression levels of these two genes were also studied in fetal tissue. METHODS: In this case control study, a total of 35 couples with at least three consecutive IRSA and 35 fertile couples were included. Genotype analysis was performed using polymerase chain reaction and Sanger sequencing. RESULTS: No statistically significant differences were found in distribution of MMP2-1306C/T and MMP9-1562C/T genotypes in the three groups between the cases and controls. CONCLUSION: Further genetic association studies on a larger number of IRSA couples, as well as evaluation of more MMP polymorphisms and their expression profiling are needed to establish the potential role of MMP polymorphisms in IRSA.

The A1298C Methylenetetrahydrofolate Reductase Gene Variant as a Susceptibility Gene for Non-Syndromic Conotruncal Heart Defects in an Indian Population.

Conotruncal heart defects (CTHDS) are a subgroup of congenital heart malformations that are considered to be a folate-sensitive birth defect. It has been hypothesized that polymorphisms in genes that code for key enzymes in the folate pathway may alter enzyme activity, leading to disruptions in folate metabolism and thus may influence the risk of such heart defects. This study was designed to investigate the association of six selected folate-metabolizing gene polymorphisms with the risk of non-syndromic CTHDs in an Indian population. This was a case-control study involving 96 cases of CTHDs and 100 control samples, ranging in age from birth to 18 years. Genotyping using Sanger sequencing was performed for six single nucleotide polymorphisms of genes involved in folate metabolism. Logistic regression analyses revealed that for the 5,10-methylenetetrahydrofolate (MTHFR) A1298C polymorphism, the CC variant homozygote genotype was associated with a significantly increased risk of CTHDs. The results of this study support an association between the inherited MTHFR A1298C genotype and the risk of CTHDs in an Indian population.

Single nucleotide polymorphisms of enamel formation genes and early childhood caries - systematic review, gene-based, gene cluster and meta-analysis.

Introduction: Genetic polymorphisms of genes regulating amelogenesis can alter susceptibility to Early Childhood Caries (ECC). This systematic review aims to analyze associations between single-nucleotide polymorphisms of enamel formation genes and ECC. Methods: Search was conducted across PUBMED, CINAHL, LILACS, SCOPUS, EMBASE, Web of Science, Genome-Wide Association Studies databases from January 2003 to September 2022. This was supplemented by hand search. Totally 7124 articles were identified and 21 articles that satisfied the inclusion criteria proceeded to data extraction. Quality assessment was done using the Q-Genie tool. Results: Quantitative synthesis revealed that homozygous genotype AA of rs12640848 was significantly higher in children with ECC with an odds ratio of 2.36. Gene-based analysis revealed significant association between six variants of AMBN, four variants of KLK4, two variants of MMP20, and a single variant of each of MMP9 and MMP13 genes and ECC. The Bonferroni corrected-log10 P value of amelogenesis gene Cluster was 2.25 (0.05/88 = 5.6 × 10-4). Search Tool for Retrieval of Interacting Genes and Proteins plot constructed to comprehend the protein-protein interaction revealed the presence of four functional clusters. Gene function prediction using Multiple Association Network Integration Algorithm revealed that physical interaction between these genes was 69.3%. Conclusion: Polymorphisms of genes regulating amelogenesis can influence the susceptibility to ECC. AA genotype of rs12640848 may increase the susceptibility to ECC. Gene-based analysis revealed a significant association between multiple polymorphisms of genes regulating amelogenesis and ECC.

Burden of Type 2 Diabetes and Associated Cardiometabolic Traits and Their Heritability Estimates in Endogamous Ethnic Groups of India: Findings From the INDIGENIUS Consortium.

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.

Clonal hematopoiesis of indeterminate potential (CHIP) and cardiovascular diseases-an updated systematic review.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of mortality in India. Residual risk exists in patients receiving optimal guideline-directed medical therapy. Possession of certain somatic mutations, at a variant allele frequency of ≥ 2% in peripheral blood, driving clonal expansion in the absence of cytopenias and dysplastic hematopoiesis is defined as clonal hematopoiesis of indeterminate potential (CHIP). Recently, it was found that carriers of CHIP had a higher risk to have coronary artery disease (CAD) and early-onset myocardial infarction. Association of CHIP with heart failure and valvular heart diseases is increasingly being considered. The common link that connects CHIP mutations and CVDs is inflammation leading to increased expression of cytokines and chemokines. We intended to do a systematic review about the association of CHIP mutations and CVD along with identifying specific CHIP mutations involved in increasing the risk of having CVDs. We performed an extensive literature search in PubMed and Google Scholar databases. Out of 302 articles, we narrowed it down to 10 studies based on our pre-specified criteria. The methodology adopted for the identification of CHIP mutations in the selected studies included - whole-exome sequencing (n = 3), whole-genome analysis (n = 1), transcriptome profiling analysis (n = 1), whole-genome analysis (n = 1), and single-cell RNA-sequencing (n = 1). We found that the available literature suggested an association between CHIP and CVD. The most commonly described CHIP mutations in patients with CVD are DNMT3A, TET2, ASXL1, TP53, JAK2, and SF3B. We further analyzed the commonly mutated CHIP genes using bioinformatics tools. Protein function and interaction analysis were performed using the g: Profiler and GeneMANIA online tools. The results revealed significant bio grid interactions for molecular functions, biological processes, and biological pathways. Interaction analysis showed significant physical and co-expression interactions. SHORT CONCLUSION: We conclude that there exists a significant association between CHIP mutations and CVD with DNMT3A, TET2, ASXL1, TP53, JAK2, and SF3B as the commonly implicated genes. The recognition of the link between CHIP and cardiovascular events will expand our understanding of residual risk and will open up new avenues of investigation and therapeutic modalities in the management of patients with CVD.

Genetic Polymorphisms in miR-146a, miR-196a2 and miR-125a Genes and its Association in Prostate Cancer.

The increase in incidence of prostate cancer in the Indian Population stresses the need to identify genetic markers for susceptibility and prognosis. Recent studies show that microRNAs play an important role in tumorigenesis by altering proliferation, differentiation and cell death. Gene polymorphisms not only in promoter region but also within miRNA gene have been shown to affect expression. The present study was aimed to analyze the role of miR-146a, miR-196a2 and miR-125a gene polymorphisms in prostate cancer. Genotyping of three SNPs rs73318382, rs57095329, rs2910164 in miRNA146a, rs11614913 in miR-196a2 and rs41275794, rs12976445, rs10404453 and rs1297533 in miR-125a was performed in 100 cases and 100 controls. Statistical analysis revealed the heterozygous AG genotype of the rs57095329 was significantly decreased in the cases when compared to the controls (OR-0.45, CI -0.24 to 0.85, p value-0.02) indicating an inverse association of this genotype with prostate cancer. Further the heterozygous CT of miR-196a2 (rs11614913) (OR-1.88, CI-1.06 to 3.35, p-0.02) and homozygous CC of miR-125a (rs12976445) (OR-2.55, CI -1.15 to 4.65, p-0.03) showed increased risk for prostate cancer. Combined analysis of all the genotypes revealed that the haplotype combination AGGCGTGG (OR = 0.09 at CI 95% (0.01-0.65) showed an inverse association with prostate cancer. Stratified analysis based on the age and tumor grade revealed no significant association.

A case-control association of RANTES (-28C >G) and CCR5-Delta32 polymorphisms with Parkinson's disease in Indians.

Recent studies have suggested that chemokines and their receptors are involved in several neurodegenerative disorders. Also, numerous lines of evidence have indicated that inflammatory processes are involved in the pathogenesis of Parkinson's disease (PD). We have examined whether single nucleotide polymorphisms at the genes encoding chemokines RANTES (-28 C > G), RANTES (-403 A > G) MCP-1 (-2518 A > G), and chemokine receptors CCR2 (+190 G > A) and CCR5 (-Δ32) were associated with sporadic PD risk in the Indian population. This pilot case-control association study included 97 PD patients and 100 control subjects, who were all genotyped with PCR-RFLP for the five polymorphisms. There was no statistically significant difference in the genotype frequencies between the cases and controls for the MCP1 (-2518 A > G), RANTES (-403 A > G) and CCR2 (+190 G > A) polymorphisms. However, the results revealed a significant difference in the frequency of the heterozygous CG genotype for the RANTES (-28 C > G) polymorphism (OR = 0.49, p = 0.03) between the cases and controls. A negative association was demonstrated in the dominant model where, compared with the GG genotype, a higher frequency of the GC + CC genotype was observed in the controls. Also, a statistically significant higher frequency of the CCR5 heterozygous genotype WT/Δ32 in the controls was observed (OR = 0.31, p = 0.04). Combined genotype analysis revealed that the allele combination of G-A-G-C of CCR2 (+190G > A), MCP-1 (-2518 A/G), RANTES (-403 A/G) and RANTES (-28 C/G) respectively had a risk association with PD (OR = 6.18, p = 0.005).

Clinical, biochemical and genetic characteristics of children with congenital adrenal hyperplasia due to 17α-hydroxylase deficiency.

Objectives Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder, that could rarely be due to 17 α-hydroxylase deficiency (17αOHD) and/or 17,20 lyase deficiency. Mutation of CYP17A1 gene causes deficiency of glucocorticoids and androgens but excess of mineralocorticoids. Lack of genital ambiguity in most children causes a delay in diagnosis even until puberty. Classical presentation with hypertension and hypokalemia is often not encountered. We intended to study the clinical, biochemical and genetic characteristics of children diagnosed with CAH due to 17αOHD. Methods Three children who were diagnosed with CAH due to 17αOHD in our institute and on follow up were included in this retrospective study. Clinical, biochemical and genetic characteristics of these children were retrieved and studied from electronic medical records. Results Two children were genetic females and one was genetic male, but all three were raised as females. All had hypertension at diagnosis except one but none had hypokalemia. All of them had mutation in the CYP17A1 gene. The two females responded well to oestrogen and progesterone and had adequate estrogenization clinically. Conclusions Even though CAH due to 17αOHD is quite rare, it should be considered while evaluating young individuals with hypogonadism, hypertension with or without hypokalemia. Lack of genital ambiguity and absence of classical signs at presentation does not rule out this not so uncommon condition and warrants follow up.

Study on the SFRP4 gene polymorphism and expression in prostate cancer.

Prostate cancer is a heterogeneous disease and considered to be the most commonly diagnosed cancer. SFRP4 gene acts as Wnt antagonist in the Wnt signalling pathway, thereby playing an important role in carcinogenesis. The aim of the present study was to investigate two single-nucleotide polymorphisms: c.958 C>A (rs1802073) and c.1019 G>A (rs1802074) in the SFRP4 gene and its expression in prostate cancer. A sample size of 100 cases and 100 age-matched controls were recruited for the study. Statistical analysis revealed the heterozygous GA genotype of rs1802074 significantly increased in cases when compared to controls. Analysis of sFRP4 expression based on the genotypes showed a significantly increased expression for the heterozygous GA and homozygous AA genotypes in cases when compared to the controls. Fold change was calculated using 2-ΔΔCT method and the results showed that there were a 3.4 and 4.5 fold increase in the sFRP4 expression for GA and AA genotypes, respectively. Our results suggest that the rs1802074 polymorphism in SFRP4 gene may be associated with the risk of prostate cancer.

Mutation Analysis Using Multiplex Ligation-Dependent Probe Amplification in Consanguineous Families in South India with a Child with Profound Hearing Impairment.

BACKGROUND: Consanguineous marriage, a common practice in South India, increase the incidence of autosomal recessive diseases such as nonsyndromic hearing loss (NSHL) in offspring. This trend was noted in the children with hearing impairment (HI) who received cochlear implants (CI) at our University hospital in Porur, Chennai, India. To ascertain the genetic etiology of HI in these patients, we performed multiplex ligation-dependent probe amplification (MLPA) analysis. METHODS: A total of 25 families who had a child with NSHL were included in the study. MLPA screening of GJB2, GJB6, and GJB3 was performed for all the recruited individuals. RESULTS: The pathogenic p.W24X* mutation of GJB2 was detected in 2 patients; both of their parents were heterozygous carriers. Both families had a second-degree consanguineous marriage. CONCLUSION: This study has important implications for molecular-diagnosis strategy and genetic counseling for families with HI in South India.