Role of TLR4 (C1196T) and CD14 (C-260T) Polymorphisms in Development of Ischemic Stroke, Its Subtypes and Hemorrhagic Stroke.

In the present study, we evaluated the association of TLR4 and CD14 polymorphisms, i.e. C1196T and C-260T, respectively, with ischemic stroke (n = 700), its subtypes and hemorrhagic stroke (n = 300) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP, and the strength of association between genotypes and stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. The results revealed a lack of association for TLR4 variant with ischemic stroke and hemorrhagic stroke, although a significant association was observed with the subtypes extracranial large artery (p = 0.008), other determined aetiology (p = 0.03) and undetermined aetiology (p = 0.01). Investigations on the variant of CD14 gene revealed negative association among ischemic stroke patients; however, a significant association was observed for hemorrhagic stroke following dominant and recessive genotypic model (p = 0.05, p = 0.02). Among ischemic stroke subtype, a significant association was observed with intracranial large artery, extracranial large artery, other determined aetiology and undetermined aetiology form of stroke (p < 0.01). Further, analysis of the CD14 variant between the two major stroke types revealed a significant difference in genotype distribution following the co-dominant genotypic model (p = 0.01).

BRIP1/FANCJ Mutation Analysis in a Family with History of Male and Female Breast Cancer in India.

Male breast cancer (MBC) is a rare and poorly studied disease that is a growing global health problem. Interestingly, both the molecular basis of MBC and its histological profile are often quite distinct from the far more prevalent female breast cancer, emphasizing the need for increased focus on MBC. Here, we present a case report of an MBC patient from India with a strong familial history of breast cancer. This patient was normal for BRCA1/2 and many other common breast cancer-associated genes. However, upon further analysis, the individual was found to possess two mutations in the DNA helicase and tumor suppressor gene BRIP1, including a silent mutation at residue 879 as well as a P919S variant. Other family members were also screened for these mutations. To the best of our knowledge, this is the first report of BRIP1 mutation in MBC in the Indian population.

Association of tinnitus and hearing loss in otological disorders: a decade-long epidemiological study in a South Indian population / Associação de zumbido e perda auditiva em distúrbios otológicos: estudo epidemiológico de uma década em uma população do Sul da Índia

Abstract Introduction: Tinnitus is a common disorder that occurs frequently across all strata of population and has an important health concern. Tinnitus is often associated with different forms of hearing loss of varying severity. Objective: The present study aimed to identify the association of tinnitus with hearing loss in various otological disorders of a South Indian population. Methods: A total of 3255 subjects referred to the MAA ENT Hospital, Hyderabad, from 2004 to 2014, affected with various otological diseases have been included in the present cross-sectional study. Diagnosis of the diseases was confirmed by an ear, nose, and throat (ENT) specialist using detailed medical and clinical examination. Statistical analysis was performed using the χ 2 test and binary logistic regression. Results: Tinnitus was observed in 29.3% (956) of the total study subjects that showed an increased prevalence in greater than 40 years of age. There was a significant increase in risk of tinnitus with middle (OR = 1.79, 95% CI = 1.02-3.16) and inner (OR = 3.00, 95% CI = 1.65-5.45) inner ear diseases. It was noted that 96.9% (n = 927) of the tinnitus subjects was associated with hearing loss. Otitis media (60.9%), presbycusis (16.6%) and otosclerosis (14.3%) are the very common otological disorders leading to tinnitus. Tinnitus was significantly associated with higher degree of hearing loss in chronic suppurative otitis media (CSOM) subjects. Conclusion: The present study could identify the most prevalent otological risk factors leading to development of tinnitus with hearing loss in a South Indian population.

Resumo Introdução: O zumbido é um distúrbio comum que ocorre com frequência em todos os estratos da população, constituindo um problema importante de saúde. O zumbido é frequentemente associado a diferentes formas de perda auditiva e sua gravidade é variada. Objetivo: O presente estudo teve como objetivo identificar a associação entre zumbido e perda auditiva em várias doenças otológicas na população do Sul da Índia. Método: No total, 3.255 indivíduos encaminhados ao Hospital MAA ENT em Hyderabad de 2004 a 2014, com diversas doenças otológicas, foram incluídos neste estudo transversal. O diagnóstico das doenças foi confirmado pelo otorrinolaringologista por meio de exames médico e clínico detalhados. A análise estatística foi realizada com o teste do χ2 e regressão logística binária. Resultados: Zumbido foi observado em 29,3% (956) do total de participantes do estudo, com maior prevalência em indivíduos com mais de 40 anos de idade. Houve um aumento significante do risco de zumbido em doenças da orelha média (OR = 1,79, IC 95% = 1,02-3,16) e interna (OR = 3,00, IC 95% = 1,65-5,45). Observamos que em 96,9% (n = 927) dos indivíduos com zumbido houve associação com perda auditiva. Conclusão: O presente estudo pôde identificar os fatores etiológicos mais prevalentes que levam ao desenvolvimento de zumbido associado à perda auditiva em uma população do Sul da Índia. Otite média (60,9%), presbiacusia (16,6%) e otosclerose (14,3%) são doenças otológicas frequentemente associadas ao zumbido. Em indivíduos com otite média crônica supurativa (OMCS), o zumbido foi significantemente associado ao maior grau de perda auditiva.

Association of APOE (E2, E3 and E4) gene variants and lipid levels in ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population.

In the present study we evaluated the association of APOE (E2/E3/E4) polymorphism with ischemic stroke (n=620), its subtypes and hemorrhagic stroke (n=250) in a South Indian population from Telangana. The genotypes were determined using PCR-RFLP while lipid levels were measured using commercially available kits. We found significant difference in the genotypic distribution between hemorrhagic stroke patients and controls for certain genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3; E4/E4 vs.E2/E4 and E3 vs. E4]. However, no significant difference was observed in genotypic distribution between ischemic stroke patients and controls. On analysing the genotypic distribution between ischemic and hemorrhagic stroke patients, statistically significant difference was observed in specific genetic models [E2/E2 vs. E2/E4; E3/E3 vs. E2/E3; E3/E3 vs. E2/E4; E4/E4 vs. E2/E3 and E4/E4 vs. E2/E4]. In ischemic stroke subtypes analysing for alleles E3 vs. E2 and E3 vs. E4, we found significant association with intracranial large artery (p=0.01), cardioembolic stroke (p=0.001 and p=0.0004) and lacunar stroke (p=0.02). Analysing the association of various genotypes with different lipid levels significant association was observed for VLDL (P=0.000) and for triglyceride (P=0.000) levels with E2/E4 and E3/E4 genotypes in ischemic stroke but not in hemorrhagic stroke. In conclusion, our results suggest that APOE polymorphism does seem to play a role in hemorrhagic stroke and also in the development of specific subtypes of ischemic stroke. Further, in ischemic stroke VLDL and triglycerides levels were found to be significantly associated with E2/E4 and E3/E4 genotypes.

Association of tinnitus and hearing loss in otological disorders: a decade-long epidemiological study in a South Indian population.

INTRODUCTION: Tinnitus is a common disorder that occurs frequently across all strata of population and has an important health concern. Tinnitus is often associated with different forms of hearing loss of varying severity. OBJECTIVE: The present study aimed to identify the association of tinnitus with hearing loss in various otological disorders of a South Indian population. METHODS: A total of 3255 subjects referred to the MAA ENT Hospital, Hyderabad, from 2004 to 2014, affected with various otological diseases have been included in the present cross-sectional study. Diagnosis of the diseases was confirmed by an ear, nose, and throat (ENT) specialist using detailed medical and clinical examination. Statistical analysis was performed using the χ2 test and binary logistic regression. RESULTS: Tinnitus was observed in 29.3% (956) of the total study subjects that showed an increased prevalence in greater than 40 years of age. There was a significant increase in risk of tinnitus with middle (OR=1.79, 95% CI=1.02-3.16) and inner (OR=3.00, 95% CI=1.65-5.45) inner ear diseases. It was noted that 96.9% (n=927) of the tinnitus subjects was associated with hearing loss. Otitis media (60.9%), presbycusis (16.6%) and otosclerosis (14.3%) are the very common otological disorders leading to tinnitus. Tinnitus was significantly associated with higher degree of hearing loss in chronic suppurative otitis media (CSOM) subjects. CONCLUSION: The present study could identify the most prevalent otological risk factors leading to development of tinnitus with hearing loss in a South Indian population.

Paternal transmission of MTHFD1 G1958A variant predisposes to neural tube defects in the offspring.

AIM: This study aimed to evaluate the role of methylenetetrahydrofolate dehydrogenase (MTHFD1) G1958A variant (rs2236225) as a 'maternal, paternal, or embryonic' genetic risk factor for neural tube defect (NTD) susceptibility. It also estimated differential associations based on type of NTD, offspring sex, maternal-paternal-offspring genotype incompatibility, and parent-of-origin effects (POE) using both case-control and family-based approach. In addition, genotype impact on serum folate levels was also assessed. METHOD: The study population (n=900) consisted of 120 NTD case-parent triads (n=120×3=360) and 180 healthy control-parent triads (n=180×3=540) from South India. Umbilical cord tissues were collected from those with NTD and control newborn infants, and blood samples from case and control parents. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis used were SPSS, transmission disequilibrium test and POE. Serum folate levels were estimated using enzyme-linked immunosorbent assay. RESULTS: In the case-control study, those with the MTHFD1 G1958A variant were associated with around twofold risk of anencephaly (p=0.01) and spina bifida (p<0.01). Among parents, fathers were associated with around twofold risk of having an offspring with anencephaly (p<0.01). Considering offspring sex, the A allele in single or double dose conferred around two- to fourfold risk of anencephaly (p=0.01), spina bifida (p<0.01), and encephalocele (p<0.05) in females only. Maternal AA genotype was not associated independently but conferred threefold risk when combined with paternal GA genotype (p=0.01). Transmission disequilibrium and POE were not observed in controls (p>0.05) but revealed excess total (odds ratio [OR]=2.21; p<0.01) and paternal transmission (OR=7.00; p<0.01) of the G1958A allele to those with spina bifida, which remained the same for female cases (total transmission OR=3.00, p=0.01; paternal transmission OR=12.00, p<0.01). Increased serum folate levels were observed in case fathers with GA and AA genotypes than control fathers (p<0.01). INTERPRETATION: Our research provides the first evidence supporting a paternal, rather than a maternal, transmission bias of MTHFD1 G1958A variant for NTD susceptibility in the offspring.

A Common SNP of IL-10 (-1082A/G) is Associated With Increased Risk of Premenopausal Breast Cancer in South Indian Women.

BACKGROUND: Evading the immune destruction and angiogenesis has been the two hallmarks of cancer. Interleukin-10 (IL-10) is a cytokine with immune suppressing (pro-tumorigenic) and anti-angiogenic (anti-tumorigenic) properties, thus making the role of IL-10 in tumorigenesis enigmatic. Previous studies have suggested a critical role of IL10 altered expression in complex process of tumor-microenvironment, co-evolution and tumorigenesis. OBJECTIVES: Evaluating the role of IL10 (-1082A/G) gene promoter polymorphism in breast cancer patients from South India. PATIENTS AND METHODS: A case-control study was conducted with a total of 285 individuals, these include 125 histologically confirmed breast cancer patients and 160 age and sex matched controls. Genotypes were determined by allele-specific polymerase chain reaction (AS-PCR), followed by agarose gel electrophoresis. Statistical analysis was done to test the significance of results obtained. RESULTS: Statistical analysis revealed that AA genotype of the Il-10 -1082A/G polymorphism is significantly associated with breast cancer (AA vs. AG: χ(2) = 14.46, P = 0.0001432, OR = 2.854, 95% CI = 1.68 - 4.849). Up on stratifying subjects based on cancer stage, age at onset, menopausal status, AA genotype has associated with all the sub groups, except for post-menopausal women. There was no significant association which was observed with respected to hormonal status (ER, PR) and Her2/neu status. CONCLUSIONS: The present study suggests that IL-10 AA genotype as a risk factor in the etiology of breast cancer in the South Indian population.

Significant Association of Interleukin4 Intron 3 VNTR Polymorphism with Susceptibility to Gastric Cancer in a South Indian Population from Telangana.

BACKGROUND: Gastric cancer (GC) is the fifth most common malignancy and remains a considerable public health burden worldwide. Genetic variations in genes encoding cytokines and their receptors influence the intensity of the Helicobacter pylori associated inflammatory response, which may contribute to individual differences in the outcome and severity of the disease. Interleukin4 is a typical pleiotropic T helper 2 (Th2) cytokine and is a critical mediator of Th1/Th2 balance. It is involved in the regulation of inflammation-mediated carcinogenesis in human organs, including gastric cancer. OBJECTIVE: The present retrospective case control study was undertaken to evaluate the association of IL4 intron 3 VNTR polymorphism with the susceptibility to GC in a south Indian population from Telangana state. MATERIALS AND METHODS: A total of 182 patients with diagnosed GC and 326 randomly selected healthy controls were enrolled in the present study. Genomic DNA was extracted from peripheral leukocytes and genotyping was determined by PCR-based assay. Association between genotypes and gastric cancer was examined by unconditional logistic regression analysis. RESULT: The variant 3R/2R and 2R/2R genotypes of IL4 exon3 VNTR polymorphism had about 1.9 fold and 3fold increased GC risk, respectively, when compared with 3R/3R genotype [3R/2R vs. 3R/3R: adjusted odds ratio (AOR) = 1.90, 95% confidence interval (CI) = 1.23-2.95 P = 0.004 and 2R/2R vs. 3R/3R: AOR (95%CI) = 2.96 (1.29-6.82), P = 0.011]. Furthermore, a significant increased risk of GC was found for the 2R allele carriers (3R/2R + 2R/2R) compared with the 3R/3R genotype (AOR (95%CI) = 2.04 (1.35-3.10), P = <0.000). The IL4 2R allele frequency was 0.28 among the GC group and 0.18 among the controls, and the difference was statistically significant (P = <0.000). CONCLUSION: The present study revealed an association of 2R allele and 2R carrier genotypes in the etiopathogenesis of GC in south Indian population.

Association of endothelial nitric oxide synthase gene T-786C promoter polymorphism with gastric cancer.

AIM: To investigate the role of endothelial nitric oxide synthase -786T > C promoter polymorphism in the etiology of gastric cancer (GC). METHODS: A total of 150 GC patients and 150 control subjects were included in the study. The information on demographic features was elicited with an informed consent from all the patients and control subjects using a structured questionnaire. Helicobacter pylori (H. pylori) infectivity status was tested in antral biopsies from all the subjects by rapid urease test following the method of Vaira et al. Genomic DNA was isolated from whole blood samples following the salting out method of Lahiri et al. Genotype analysis of the rs2070744 polymorphism was carried out by allele-specific polymerase chain reaction method. The genotypes were determined based on the appearance of bands on an agarose gel stained with ethidium bromide under ultraviolet gel documentation with the help of 100 bp ladder. Odds ratios and corresponding 95%CIs were determined using java stat online software. RESULTS: There was a significant difference in the distribution of C allele (C vs T; P = 0.000, OR = 5.038) in patient group compared to the control subjects exhibiting a fivefold increased risk for GC. When the T/T and C/C genotypes were compared, there was an enhanced GC risk for individuals with C/C genotype (T/T vs C/C; P = 0.000). Among the demographic factors, smoking and alcoholism were the common risk factors in patients compared to the control subjects (P < 0.05). Patients with smoking and alcoholism developed cancer even in heterozygous T/C condition (smoking: P = 0.020 and alcoholism: P = 0.005). Individuals with H. pylori infection showed seven fold increased risk for cancer. All the patients with C/C genotype revealed a significant association between H. pylori infection and GC. Among the patients 2.4% of them revealed familial incidence of GC. No significant difference was noticed between cases and controls with regard to consanguinity (P = 0.473). CONCLUSION: The Present data suggest that eNOS-786 C/C genotype and C allele may be considered as potential risk factors in patients with GC.

Role of IL-6 -174(G/C) promoter polymorphism in the etiology of early-onset preeclampsia.

OBJECTIVE: To investigate the relationship between IL-6 -174G/C promoter polymorphism and preeclampsia. METHODS: A total of 140 preeclamptic women and 135 women with normal pregnancy were considered for the present study. A standard amplification refractory mutation system PCR was carried out for genotyping of IL-6 G-174C promoter polymorphism. Genotypic distribution was compared with values predicted by Hardy-Weinberg equilibrium using χ (2) test. Odds ratios and their respective 95 % confidence intervals were used to measure the strength of association. RESULTS: The frequencies observed, CC, GC and GG, were 53.5, 26.6 and 20 % in patients and 26.6, 23.7 and 49.6 % in the controls. There is a significant difference in the distribution of genotypes and alleles of IL-6 G-174 C between the two groups. CONCLUSION: The present study suggests that the IL-6 -174 promoter polymorphism is a major genetic regulator in the etiology of early-onset preeclampsia.

A Rare De Novo Balanced X; 1 Translocation in an Indian Female with Primary Amenorrhea.

BACKGROUND: Translocations involving X chromosome and an autosome are rather rare due to associated infertility in men and subfertility in women. X chromosome translocations are frequently associated with primary or secondary amenorrhea. In this report, a case of primary amenorrhea with a de novo balanced reciprocal translocation was presented between chromosomes X and 1. CASE PRESENTATION: A 24 year-old proposita with the complaint of primary amenorrhea was found to have hypoplastic uterus and streak gonads with a normal hormonal profile. Chromosomal analysis of the proband revealed a de novo translocation of 46, X, t(X; 1) (q21; p32) chromosomal constitution. Parental karyotypes of the proband showed normal karyotype. CONCLUSION: The observed translocation between chromosome X and 1 in the patient suggest either the disruption of a critical gene expression due to position effect or deletion of one or more essential genes in the disrupted long arm of the affected X chromosome. To the best of our knowledge, this is the first report from our ethnic group.

Interleukin 1ß (+3954, -511 and -31) polymorphism in chronic periodontitis patients from North India.

OBJECTIVE: Several studies have implicated the role of interleukin-1 in various chronic diseases including periodontitis. The present study was carried out with an aim to evaluate the role of interleukin 1ß polymorphisms, namely +3954C/T, -511C/T and -31T/C, in the development of chronic periodontitis. MATERIALS AND METHODS: Twenty-nine chronic periodontitis patients and 31 healthy controls of North Indian origin from Chhattisgarh were recruited for the study. The genotypes for the three variants were determined using the PCR-RFLP technique and the strength of association between genotypes and periodontitis was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. RESULTS: Analysis for the +3954 allelic and genotypic frequencies of the polymorphism revealed a significant difference in the CT genotype between periodontitits patients and controls (p = 0.03). A significant difference was also observed in the allelic frequencies between the two groups (p = 0.02). For the -511 site, TT genotype revealed a significant association with the disease (p = 0.01). A significant association was also found following the co-dominant model (p = 0.007). However, the -31 polymorphism revealed no significant difference between patients and controls. CONCLUSIONS: In conclusion, the present study suggests a strong association of the TT genotype of -511 and CT genotype of +3954 variant of interleukin 1ß with chronic periodontitis. However, the -31 variant did not show a significant association with the disease.

Association of ACE gene I/D polymorphism and ACE levels with hemorrhagic stroke: comparison with ischemic stroke.

In the present study, we investigated the association of insertion/deletion polymorphism of ACE gene with genetic predisposition to hemorrhagic stroke and also determined the mean ACE activity levels in ischemic and hemorrhagic stroke patients. Two hundred hemorrhagic stroke, 200 ischemic stroke patients and 200 gender and age matched controls were recruited for the study. We found statistically significant difference in the genotypic distribution between hemorrhagic patients and controls for dominant, co-dominant and recessive models. Significant difference was observed in the allelic frequencies between hemorrhagic patients and controls. Multiple logistic regression analysis confirmed these findings [adjusted OR for DD genotype was 2.46 (95 % CI 1.43-4.21) and p = 0.001] and [adjusted OR for ID genotype was 5.45 (95 % CI 2.6-10.4) and p = 0.001]. We have already established the association of this polymorphism in ischemic stroke patients. Comparing hemorrhagic with ischemic stroke, we found a significant difference in genotypic distribution between the two [for II vs. DD, χ (2) = 4.75; p = 0.03, OR = 0.5 (95 % CI 0.27-0.93) and for DD vs. ID, χ (2) = 5.1; p = 0.02, OR = 1.8 (95 % CI 1.1-3.3)]. Our results indicate that DD genotype and D allele are important risk factors for the development of stroke. Individuals harboring DD genotype of ACE I/D polymorphism are more predisposed to hemorrhagic stroke than ischemic stroke. Further, the mean ACE activity level was found to be significantly higher in hemorrhagic and ischemic stroke in comparison with controls, but there was no significant difference in the levels found between the two types of stroke.

Association of -1382A>G CCL11 gene variant with ischemic stroke, its subtypes and hemorrhagic stroke in a South Indian population.

BACKGROUND: CCL11 (Eotaxin-1) is an important inflammatory cytokine belonging to the CC family of chemokines associated with a number of infection or inflammation-related diseases such as atherosclerosis and stroke. We investigated the association of CCL11 gene polymorphism rs4795895-1382A>G with ischemic and hemorrhagic stroke. MATERIALS AND METHODS: Six hundred and twenty ischemic stroke patients, 620 age- and sex-matched healthy controls, and 220 hemorrhagic stroke patients, 220 age- and sex-matched healthy controls were included in the present study. The CCL11 gene polymorphism rs4795895-1382A>G was determined using PCR-RFLP technique. RESULTS: We found a statistically significant difference in the genotypic distribution between ischemic stroke patients and controls (For GG vs. AA, χ² = 7.604; P < 0.001, Odds ratio = 2.793; 95% CI = 1.308-5.9). For GG vs. AA + AG, χ² = 44.8, P < 0.001, Odds ratio = 2.382 (95% CI = 1.842-3.081). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, χ² = 43.26; P < 0.001, Odds ratio = 2.127; 95% CI = 1.693-2.672). Statistically significant difference was observed in the genotypic distribution between hemorrhagic stroke patients and controls (For GG vs. AG, χ² = 26.78; P = 0.001, Odds ratio = 3.5; 95% CI = 2.162-5.824). A significant difference was observed in the frequency of G and A alleles in patients and controls (For G vs. A, χ² = 41.98; P = 0.001, Odds ratio = 4.1; 95% CI = 2.61-6.44). CONCLUSION: The results of the present study show that the GG genotype is a significant risk factor for ischemic as well as hemorrhagic stroke. Further, the frequency of the GG genotype was observed to be higher in hemorrhagic stroke patients in comparison with ischemic stroke. Evaluating the association with ischemic stroke subtypes, a significant association was observed with intracranial large artery atherosclerosis and lacunar stroke.

E-selectin gene (S128R) polymorphism in hemorrhagic stroke: comparison with ischemic stroke.

Increasing evidence suggests that genetic variation in inflammatory genes plays a pivotal role in pathogenesis of stroke. The aim of the present study was to evaluate the association of E-selectin S128R polymorphism with hemorrhagic stroke and also to evaluate the genotypic and allelic variation with ischemic stroke in a South Indian population from Andhra Pradesh. In this study, we recruited 250 hemorrhagic stroke patients along with 250 age and sex matched controls. The genotypes were determined using PCR-RFLP method and the strength of association between genotypes and hemorrhagic stroke was determined by odds ratio with 95% confidence interval (CI) and chi-square analysis. Allelic and genotypic frequencies of the polymorphism differed significantly between hemorrhagic stroke patients and controls (p<0.001). Significant association was also found following dominant (p<0.001) and co-dominant (p<0.001) models. On comparing the genotypic and allelic frequencies between ischemic and hemorrhagic stroke significant difference was found between the two stroke types (p<0.001). In conclusion, we found the AC genotype to be a significant risk factor for hemorrhagic stroke and we also found significant differences in AC genotype and C allele among the two stroke types. The genotypic and allelic variation between the ischemic and hemorrhagic stroke, suggests that E-selectin S128R mediated amplification of leukocytes onto endothelial cells, leading to secondary damage of brain cells is more pronounced in hemorrhagic stroke.

A novel androgen receptor gene mutation in a patient with congenital adrenal hyperplasia associated with penoscrotal hypospadias.

Congenital adrenal hyperplasia (CAH) associated with penoscrotal hypospadias is a rare case of disorders of sex development. Here, we report clinical, genetic, biochemical, and molecular findings in a 2-year-old infant with CAH and penoscrotal hypospadias. Chromosomal analysis revealed 46,XX karyotype. Hormonal investigations indicated low levels of cortisol and elevated levels of testosterone, 17-hydroxyprogesterone, and androstenedione hormone. Molecular genetic testing of androgen receptor (AR) gene identified a novel homozygous missense mutation of single nucleotide transition G to A at position 2058 (GenBank accession number GU784855), resulting in amino acid interchange alanine to threonine at codon 566 in exon 2 (Ala566Thr) (GenBank Protein_id ADD26777.1). The nature of the mutation presented is in the highly conserved DNA-binding domain of the AR gene. The novel mutation identified in the rare genetic disorder provides additional support to the previously reported genotype-phenotype correlations, and our finding has expanded the spectrum of known mutations of the AR gene.

CRP gene (1059G>C) polymorphism and its plasma levels in ischemic stroke and hemorrhagic stroke in a south Indian population.

In the present study, we evaluated the association of 1059G>C polymorphism in C-reactive protein (CRP) gene with the risk of ischemic and hemorrhagic strokes. We did not find a significant association of this polymorphism with stroke. However, 2 % of mutants were observed in hemorrhagic stroke patients with a 0.01 frequency for the C allele. We also estimated the high-sensitivity C-reactive protein (hsCRP) levels in hemorrhagic stroke and compared the levels with our already published data on ischemic stroke. The hsCRP level in hemorrhagic stroke was found to be significantly elevated in comparison with that in controls (p<0.001). However, there was no difference in the mean value of hsCRP levels between types of stroke. In conclusion, the G>C polymorphism in the promoter region of the CRP gene is not abundant in the population and cannot be connected with different hsCRP levels and stroke prediction. The CRP level is a useful marker in stroke, but cannot help in differentiating between types of stroke.

Role of IL-10 -819(t/c) promoter polymorphism in preeclampsia.

Preeclampsia is a severe complication of pregnancy characterized by an excessive maternal systemic inflammatory response with activation of both the innate and adaptive immune system. Interleukin-10 affects maternal intravascular inflammation, as well as endothelial dysfunction. The aim of the study was to investigate the association between IL-10 T-819 C polymorphism and preeclampsia. A total of 120 pregnant women with preeclampsia and 120 women with normal pregnancy attending the Gynecological Unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the present study. A standard amplification refractory mutation system (ARMS) PCR was carried out for genotyping of IL-10 T-819 C promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups was compared with values predicted by the Hardy-Weinberg equilibrium using χ2 test. Odds ratios (OR) and their respective 95 % confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. The frequencies of IL-10 T-819 C genotypes, CC, CT, and TT, were 47.5, 28.3, and 24.2 % in women with preeclampsia and 20.8, 48.3, and 30.8 % in the controls, respectively. There is a significant difference in the distribution of genotypes and alleles of IL-10 T-819 C between the two groups (test power = 0.66). The present study suggests that the IL-10 T-819 C gene promoter polymorphism can be a major genetic regulator in the etiology of preeclampsia.

A novel insertion-induced frameshift mutation of the androgen receptor gene in a patient with primary amenorrhea.

OBJECTIVE: To report a novel single nucleotide insertion mutation, and present the clinical, genetic, biochemical findings in a patient with primary amenorrhea. METHODS: Chromosomal analysis was performed by harvesting lymphocytes from peripheral blood sample. Hormonal analysis was performed from the serum. After genomic DNA extraction from peripheral blood leukocytes the coding regions and corresponding exon-intron boundaries of sex-determining region Y (SRY) gene and androgen receptor (AR) gene were amplified by PCR and subjected to direct sequencing. RESULTS: In the patient with a karyotype 46,XX, we identified a novel single nucleotide insertion mutation of the nucleotide G at position 2369 (GenBank accession number HM010955), resulting in amino acid interchange cysteine to tryptophan at codon 669 in exon 4 [Cys669Trp] (GenBank Protein_id ADF47187). CONCLUSIONS: We report a novel single nucleotide insertion mutation in exon 4 region of the AR gene. The nature of the mutation presented in the patient is in the ligand-binding domain (LBD) of the AR gene. This insertion mutation was predicted to produce frame shift mutation and resulted in truncated form of the AR protein, implicating it in the phenotype observed with primary amenorrhea.

Evaluation of Interleukin-10 (G-1082A) Promoter Polymorphism in Preeclampsia.

BACKGROUND: Preeclampsia is a pregnancy-specific syndrome that may be life-threatening, especially to the fetus. Several causes have been reported that may have a possible role in the development of the disorder. Interleukin-10 affect maternal intravascular inflammation, as well as endothelial dysfunction. The aim of this study was to investigate the association between IL-10 G-1082A polymorphism and preeclampsia. METHODS: A total of eighty-eight pregnant women with preeclampsia and 100 women with normal pregnancy attending the Gynecological unit of Government Maternity Hospital, Petlaburz, Hyderabad, India, were considered for the study. A standard amplification refractory mutation system (ARMS) PCR was carried out for genotyping IL-10 G-1082A promoter polymorphism in all the participants. Genotypic distribution of the control and patient groups were compared with values predicted by Hardy-Weinberg equilibrium using χ(2) test. Odd ratios (OR) and their respective 95% confidence intervals were used to measure the strength of association between IL-10 gene polymorphism and preeclampsia. RESULTS: The frequencies of IL-10 G-1082A genotypes, GG, GA and AA, were 17.8%, 41.09% and 41.09% in women with preeclampsia and 25%, 28% and 47% in the controls respectively. There was no significant difference in the distribution of genotypes and alleles of IL-10 G-1082A between the two groups (Test power=0.66). CONCLUSION: The present study suggests that the IL-10 G-1082A gene promoter polymorphism is not a major genetic regulator in the etiology of preeclampsia.