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Suraksha Agrawal

Publications and source records attributed to Suraksha Agrawal.

At least 19 recordsLinked to original sources
PubMed2006

Fertility in men with Down syndrome: a case report.

OBJECTIVE: To inform clinicians about fertility in males with Down syndrome. DESIGN: Case report. SETTING: Medical Genetics Department of a tertiary-care hospital. PATIENT(S): A 26-year-old man with confirmed nonmosaic trisomy 21. INTERVENTION(S): Karyotype, amniocentesis, paternity testing using microsatellite markers. MAIN OUTCOME MEASURE(S): Confirmed paternity in the son of a male with nonmosaic trisomy 21. RESULT(S): A male with nonmosaic Down syndrome fathered a normal son, and the paternity was proven by microsatellite marker analysis. CONCLUSION(S): Although Down syndrome males have been reported to be infertile, it may not always be true. Infertility in males has been attributed to defective spermatogenesis, but ignorance of the sexual act may be one of the contributing factors. It is important to advise postpubertal Down syndrome males on contraceptive measures.

Adult↗
PubMed2006

High prevalence of ACE DD genotype among north Indian end stage renal disease patients.

BACKGROUND: The Renin-Angiotensin system (RAS) is a key regulator of both blood pressure and kidney functions and their interaction. In such a situation, genetic variability in the genes of different components of RAS is likely to contribute for its heterogeneous association in the renal disease patients. Angiotensin converting enzyme-1 (ACE-1) is an important component of RAS which determines the vasoactive peptide Angiotensin-II. METHODS: In the present study, we have investigated 127 ESRD patients and 150 normal healthy controls from north India to deduce the association between ACE gene polymorphism and ESRD. The inclusion criteria for patients included a constantly elevated serum creatinine level above normal range (ranging from 3.4 to 15.8) and further the patients were recommended for renal transplantation. A total of 150 normal healthy controls were also genotyped for ACE I/D polymorphism. The criterion of defining control sample as normal was totally based on the absence of any kidney disease determined from the serum creatinin level. Genotyping of ACE I/D were assayed by polymerase chain reaction (PCR) based DNA amplification using specific flanking primers Based on the method described elsewhere. RESULTS: The difference of DD and II genotypes was found highly significant among the two groups (p = 0.025; OR = 3.524; 95% CI = 1.54-8.07). The combined genotype DD v/s ID+II comparison validated that DD genotype is a high risk genotype for ESRD (p = 0.001; OR = 5.74; 95% CI limit = 3.4-8.5). However, no correlation was obtained for different biochemical parameters of lipid profile and renal function among DD and non DD genotype. Interestingly, approximately 87% of the DD ESRD patients were found hypertensive in comparison to the 65% patients of non DD genotype CONCLUSION: Based on these observations we conclude that ACE DD genotype implicate a strong possible role in the hypertensive state and in renal damage among north Indians. The study will help in predetermining the timing, type and doses of anti-hypertensive therapy for ESRD patients.

Adult↗
PubMed2006

Comment on "Reconstructing the origin of Andaman islanders".

On the basis of mitochondrial DNA sequence analyses, Thangaraj et al. (Brevia, 13 May 2005, p. 996) proposed that Andaman islanders descended from the first humans to migrate out of Africa. We identified mitochondrial DNA from two northeast Indian Rajbanshi individuals that shares three specific mutations with the M31a lineage observed in the Great Andamanese, which suggests that the predecessor of haplogroup M31 originated on the Indian subcontinent.

Africa↗
PubMed2006

Genetic predisposition and renal allograft failure: implication of non-HLA genetic variants.

Renal allograft rejection or dysfunction often results in graft failure, and remains the major obstacle in the success of renal transplantation. Various immunological and nonimmunological factors are involved in allograft rejection. In addition to human leukocyte antigen loci, several genetically controlled molecules have been identified in recent years as playing important roles in the process of rejection. Genetic variants in genes encoding different T-helper (Th) type 1 and Th2 cytokines, chemokines and their receptors, growth factors, molecules of the renin-angiotensin system, enzymes of the homocysteine pathway, and proteins acting as substrates of immunosuppressive drugs impact on the success of engraftment and highlight the concept of genetic predisposition to allograft rejection. This review evaluates specific genetic variants and their functional roles in graft failure, with an emphasis on the latest methodologies available for genotyping, and appropriate strategies to enable them to become a tool of predictive and individualized medicine to ensure better transplant outcome.

Genetic Predisposition to Disease↗
PubMed2006

Non-classical HLA-G antigen and its role in the cancer progression.

Various changes take place during the progression of cancer, some of which are favorable for tumor development and may help to escape the immunosurvillance. These include changes in the microenvironment around the developing tumor, which could be produced in response to phenotypic alterations or could modulate the expression of certain markers of tumor development. One such newly discovered molecule is HLA-G, which has been found to have immunosuppressive and immunomodulatory roles in the cancer development. The regulatory sequences, as seen, may be induced by various factors that may be present in tumor microenvironment. A recent study has investigated the antigen -G as a marker of susceptibility to chemotherapy. Further, its expression on tumors and how it can be exploited for diagnosis and therapy is discussed in this article.

Biomarkers, Tumor↗
PubMed2006

S252W mutation in Indian patients of Apert syndrome.

Two common mutations in the exon IIIa of fibroblast growth factor receptor 2 account for majority of the cases of Apert syndrome. They can be analyzed by amplifying the segment followed by testing for the abolition of restriction sites. We evaluated two children with typical features of Apert syndrome. A segment of FGFR2 exon IIIa was amplified by polymerase chain reaction. Restriction fragment length polymorphism was analyzed using enzymes MboI and BglI respectively for S252W and P253R mutations. The DNA segment was sequenced using ABI 310 automated DNA fragment analyzer. Both the patients showed S252W mutations. DNA sequencing confirmed the results of the restriction fragment length polymorphism. Our study is the first report from Indian subcontinent to show the prevalence of S252W mutation among Apert syndrome patients from Indian origin.

Acrocephalosyndactylia↗
PubMed2005

The dazzling array of basal branches in the mtDNA macrohaplogroup M from India as inferred from complete genomes.

Many efforts based on complete mitochondrial DNA (mtDNA) genomes have been made to depict the global mtDNA landscape, but the phylogeny of Indian macrohaplogroup M has not yet been resolved in detail. To fill this lacuna, we took the same strategy as in our recent analysis of Indian mtDNA macrohaplogroup N and selected 56 mtDNAs from over 1,200 samples across India for complete sequencing, with the intention to cover all Indian autochthonous M lineages. As a result, the phylogenetic status of previously identified haplogroups based on control-region and/or partial coding-region information, such as M2, M3, M4, M5, M6, M30, and M33, was solidified or redefined here. Moreover, seven novel basal M haplogroups (viz., M34-M40) were identified, and yet another five singular branches of the M phylogeny were discovered in the present study. The comparison of matrilineal components among India, East Asia, Southeast Asia, and Oceania at the deepest level yielded a star-like and nonoverlapping pattern, reflecting a rapid mode of modern human dispersal along the Asian coast after the initial "out-of-Africa" event.

DNA, Mitochondrial↗
PubMed2005

Extensive genomic and functional polymorphism of the complement control proteins.

Using combinations of genomic markers, we describe more than 20 distinct ancestral haplotypes (AH) of complement control proteins (CCPs), located within the regulators of complement activation (RCA) alpha block at 1q32. This extensive polymorphism, including functional sites, is important because CCPs are involved in the regulation of complement activation whilst also serving as self and viral receptors. To identify haplotypes, we used the genomic matching technique (GMT) based on the pragmatic observation that extreme nucleotide polymorphism is packaged with duplicated sequences as polymorphic frozen blocks (PFB). At each PFB, there are many alternative sequences (haplotypes) which are inherited faithfully from very remote ancestors. We have compared frequencies of RCA haplotypes and report differences in recurrent spontaneous abortion (RSA) and psoriasis vulgaris (PV).

Amino Acid Sequence↗
PubMed2005

Reconstructing recent human phylogenies with forensic STR loci: a statistical approach.

BACKGROUND: Forensic Short Tandem Repeat (STR) loci are effective for the purpose of individual identification, and other forensic applications. Most of these markers have high allelic variability and mutation rate because of which they have limited use in the phylogenetic reconstruction. In the present study, we have carried out a meta-analysis to explore the possibility of using only five STR loci (TPOX, FES, vWA, F13A and Tho1) to carry out phylogenetic assessment based on the allele frequency profile of 20 world population and north Indian Hindus analyzed in the present study. RESULTS: Phylogenetic analysis based on two different approaches - genetic distance and maximum likelihood along with statistical bootstrapping procedure involving 1000 replicates was carried out. The ensuing tree topologies and PC plots were further compared with those obtained in earlier phylogenetic investigations. The compiled database of 21 populations got segregated and finely resolved into three basal clusters with very high bootstrap values corresponding to three geo-ethnic groups of African, Orientals, and Caucasians. CONCLUSION: Based on this study we conclude that if appropriate and logistic statistical approaches are followed then even lesser number of forensic STR loci are powerful enough to reconstruct the recent human phylogenies despite of their relatively high mutation rates.

Forensic Anthropology↗
PubMed2005

An update in recurrent spontaneous abortion.

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive pregnancy losses prior to the 20th week of gestation. The etiology of recurrent spontaneous abortion is often unclear and may be multifactorial, with much controversy regarding diagnosis and treatment. Reasonably accepted etiologic causes include, genetics, anatomical, endocrine, placental anomalies, hormonal problems, infection, smoking and alcohol consumption, exposure to environmental factors, psychological trauma and stressful life event, certain coagulation and immunoregulatory protein defects. Detection of an abnormality in any of these areas may result into specific therapeutic measures, with varying degrees of success. However, the majority of cases of RSA remains unexplained and is found to be associated with certain autoimmune (APA, ANA, ACA, ATA, AECA) and alloimmune (APCA, Ab2, MLR-Bf) antibodies that may play major role in the immunologic failure of pregnancy and may lead to abortion. Alteration in the expression of HLA-G molecules, T-helper-1 (Th-1) pattern of cytokines and natural killer (NK) cells activity may also induce abortion. Various forms of treatment like antithrombotic therapies such as aspirin and heparin, intravenous immunoglobulin (IVIg) therapy, immunotherapy with paternal lymphocytes and vitamin D3 therapy are effective mode of treatment for unexplained cause of fetal loss in women with RSA.

Abortion, Habitual↗
PubMed2005

TNFR2 gene polymorphism in coronary artery disease.

BACKGROUND: Recently atherosclerosis and coronary artery disease (CAD) are considered to be inflammatory diseases. The genetic polymorphism in inflammatory markers has been well studied and found to be associated with development of CAD. AIM: To study the association of biallelic polymorphism at position 196 in exon 6 of tumor necrosis factor 2 (TNFR2) gene and coronary artery disease. SETTINGS AND DESIGN: The study design was a prospective case control study conducted at a tertiary referral center mainly catering to the north Indian population. MATERIALS AND METHODS: One hundred and fifty angiographically proven patients with coronary artery disease and one hundred and fifty age matched controls were genotyped for TNFR2 gene by polymerase chain reaction followed by analysis of restriction fragment length polymorphism. STATISTICAL ANALYSIS: Genotype frequencies were compared in patients and controls by Chi-square test. Binary logistic regression analysis was used to examine the relationship between genotypes and disease, incorporating other variables into the model. RESULTS: The incidence of CAD in those with MM genotype was 65% and in those with RM genotype was 42%. Genotype frequency shows significant association of MM genotype with development of CAD (P < 0.001; odds ratio-2.585; 95% confidence interval 1.533-4.359). The association of TNFR2 genotype with CAD persisted on logistic regression analysis. CONCLUSION: MM genotype of TNFR2 gene is associated with development of CAD and RM genotype appears to be protective.

Adolescent↗
PubMed2004

Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia.

To resolve the phylogeny of the autochthonous mitochondrial DNA (mtDNA) haplogroups of India and determine the relationship between the Indian and western Eurasian mtDNA pools more precisely, a diverse subset of 75 macrohaplogroup N lineages was chosen for complete sequencing from a collection of >800 control-region sequences sampled across India. We identified five new autochthonous haplogroups (R7, R8, R30, R31, and N5) and fully characterized the autochthonous haplogroups (R5, R6, N1d, U2a, U2b, and U2c) that were previously described only by first hypervariable segment (HVS-I) sequencing and coding-region restriction-fragment-length polymorphism analysis. Our findings demonstrate that the Indian mtDNA pool, even when restricted to macrohaplogroup N, harbors at least as many deepest-branching lineages as the western Eurasian mtDNA pool. Moreover, the distribution of the earliest branches within haplogroups M, N, and R across Eurasia and Oceania provides additional evidence for a three-founder-mtDNA scenario and a single migration route out of Africa.

Base Sequence↗
PubMed2004

Induction of MLR-Bf and protection of fetal loss: a current double blind randomized trial of paternal lymphocyte immunization for women with recurrent spontaneous abortion.

The present study was conducted to evaluate the efficacy of paternal lymphocyte (PL) immunotherapy and its relation with the development of mixed lymphocyte reaction blocking antibodies (MLR-Bf) and the success of pregnancy outcome in women with recurrent spontaneous abortion (RSA). A total of 124 women with unknown causes of abortions was registered for immunotherapy under double blind randomized trial by using the list of computer-generated numbers. Each 5 x 10(6) autologous lymphocyte (AL), third party lymphocyte (TPL) and PL was dissolved separately in 1 ml of sterile normal saline (NS). Each 1 ml of cell suspension and neat NS was injected in women with RSA through intramuscular (250 microl), intradermal (250 microl), subcutaneous (250 microl) and intravenous (250 microl) routes. All women participants with RSA received six identical immunizations at the regular interval of 4 weeks, and were then screened for the development of MLR-Bf after the completion of immunization course, and also at the first, second and third trimesters (12th, 24th and 36th weeks) of pregnancy. However, nonimmunized MLR-Bf positive women with RSA did not receive any kind of therapy (NT) and were used as one of the control group in the present study. We have observed that PL-immunized women with RSA showed a significantly increased level of MLR-Bf (>30) and pregnancy success (84%) as compared to those women with RSA who received either AL (33%), TPL (31%), NS (25%) or those who did not receive any kind of treatment (NT, 44%; P<0.001). Our results indicated the importance of immunotherapy with PL in women with RSA and also showed that MLR-Bf can be considered as one of the important factors for pregnancy improvement.

Abortion, Habitual↗
PubMed2004

Use of ApoB' hyper variable region in studying mixed chimerism and maternal contamination in North Indian populations.

ApoB3' hyper variable region is one of the highly polymorphic genetic marker and reveals a high degree of allelic variation in different populations therefore; it can be a useful marker for different clinical tests in which individual differences at DNA level form the basis of detection. In the present study we compared Apo B3 HVR with other 28 STR markers at allele frequency level, heterozygosity, polymorphism information content (PIC) and power of exclusion. Our results indicated a high degree of heterozygosity, PIC and power of exclusion for Apo B3 HVR. These criteria lead us to investigate this marker for different purposes like detection of maternal contamination in chorionic villus samples and chimerism studies after the engraftment of bone marrow in bone marrow transplantation patients. The utility of this marker has been discussed in comparison of other markers.

Apolipoproteins B↗
PubMed2004

Short tandem repeat technology has diverse applications: individual identification, phylogenetic reconstruction and chimerism based post haematopoietic stem cell transplantation graft monitoring.

BACKGROUND: Short Tandem Repeat (STR) loci are widely considered to be effective for variety of applications including forensic applications, phylogenetic reconstruction and chimerism based post Haematopoietic Stem Cell Transplantation (HSCT) graft monitoring. For each application, specific sets of STR loci are used. AIMS: In the present study, we have attempted to use same set of STR loci for varied purposes based on their efficacy and informativity. SETTINGS AND DESIGN: Population and patient based study. MATERIALS AND METHODS: We have analyzed 5 STR loci--vWA, Tho1, FES, F13 and TPOX in 1000 North Indians. All five markers were also analyzed for chimerism based graft monitoring after HSCT in 42 HLA matched pair of patient-donor to predict the outcome of transplantation. STATISTICAL ANALYSIS: The analysis was done for Hardy Weinberg equilibrium (HWE), Heterozygosity, Polymorphism information content (PIC) and Power of Exclusion and Phylogenetic assessment. RESULTS AND CONCLUSIONS: High allelic variability in term of Heterozygosity (0.68-0.76), PIC (0.66-0.74) and high Power of exclusion (0.28-0.38) indicating high forensic utility. The ensuing PC plots finely resolved three basal clusters corresponding to three geo-ethnic groups of African, Orientals, and Caucasians. In post HSCT chimerism analysis, it was found that together these markers were informative in 38 pairs (98%) and were able to predict the chimerism status successfully. There is a possibility that these STR loci along with forensic and phylogenetic importance, can predict the outcome of HSCT successfully.

Gene Frequency↗
PubMed2003

Lymphocyte immunotherapy and its probable mechanism in the maintenance of pregnancy in women with recurrent spontaneous abortion.

INTRODUCTION: Most women with alloimmune cause of recurrent spontaneous abortion (RSA) includes increased sharing of human leukocyte antigens (HLA) that may prohibit the mother from making anti-paternal cyto-toxic antibodies (APCA), anti-idiotypic antibodies (Ab2) and mixed lymphocyte reaction blocking antibodies (MLR-Bf). Overactivity of T helper-1 (Th-1) cytokines and natural killer (NK) cells have been also reported to be the major alloimmune cause of recurrent spontaneous abortion (RSA). It was revealed from extensive updated analysis of this subject that paternal lymphocytes immunotherapy may play a significant role in the prevention of alloimmune cause of fetal loss in women with RSA. These alloimmune parameters are found to be suppressed in successful immunotherapy, which is comparable to normal pregnancy. REVIEW AND DISCUSSION: Various studies represented that paternal lymphocyte immunotherapy was attributed to the high expression of APCA, Ab2, MLR-Bf and inhibition of Th-1 pattern of cytokines and NK cell activity in women with alloimmune cause of RSA. Present updated randomized clinical trials demonstrated that women with RSA of study group who have been treated with paternal lymphocyte immunotherapy had more successful outcomes (68%) as compared to women with RSA of control group who either received autologous lymphocytes/third party lymphocytes/normal saline or no therapy (54%), ( p<0.02). However, when the results of the randomized and nonrandomized studies were pooled together it was observed that 67% of women with RSA of study group who received paternal lymphocyte immunotherapy showed successful pregnancy outcome in comparison to 36% success in women with RSA of control group who either received autologous lymphocytes/third party lymphocytes/normal saline or no therapy ( p<0.05). CONCLUSION: These results advocate the role of paternal lymphocyte immunotherapy for the maintenance of pregnancy in women with RSA.

Abortion, Habitual↗