Meka Aruna

HLA-G polymorphism patterns show lack of detectable association with recurrent spontaneous abortion.

Human leukocyte antigen-G (HLA-G) is a class I non-classical molecule that is predominantly expressed on the extravillous cytotrophoblasts at foetal-maternal interface during pregnancy. We recruited 143 recurrent spontaneous abortion (RSA) and 150 control couples for the study. DNA-based typing of the HLA-G was carried out to explore if we can validate the patterns of association reported elsewhere or find association of novel HLA-G alleles with RSA in the Indian population. We also evaluated the role of allele sharing in couples with RSA. We did not find association of any of the HLA-G alleles with RSA in our study. There is a general trend of increase in sharing among the RSA couples, but the increase is not significant. The results suggest that the HLA-G alleles or the allele sharing by couples may not play a significant role in the manifestation of RSA in the Indian context albeit more studies are required before making any definitive statement.

Role of Androgen Receptor CAG Repeat Polymorphism and X-Inactivation in the Manifestation of Recurrent Spontaneous Abortions in Indian Women

The aim of the present study was to investigate the role of CAG repeat polymorphism and X-chromosome Inactivation (XCI) pattern in Recurrent Spontaneous Abortions among Indian women which has not been hitherto explored. 117 RSA cases and 224 Controls were included in the study. Cases were recruited from two different hospitals - Lakshmi Fertility Clinic, Nellore and Fernandez Maternity Hospital, Hyderabad. Controls were roughly matched for age, ethnicity and socioeconomic status. The CAG repeats of the Androgen Receptor gene were genotyped using a PCR-based assay and were analysed using the GeneMapper software to determine the CAG repeat length. XCI analysis was also carried out to assess the inactivation percentages. RSA cases had a significantly greater frequency of allele sizes in the polymorphic range above 19 repeats (p = 0.006), which is the median value of the controls, and in the biallelic mean range above 21 repeats (p = 0.002). We found no evidence of abnormal incidence of skewed X-inactivation. We conclude that longer CAG repeat lengths are associated with increased odds for RSA with statistical power estimated to be ∼90%.

Novel alleles of HLA-DQ and -DR loci show association with recurrent miscarriages among South Indian women

BACKGROUND In this study, recurrent miscarriages (RMs) are defined as loss of two or more clinically detectable pregnancies before 20 weeks of gestation. HLA has been thought to play a role in RM. However, the results of earlier studies on the role of different human leucocyte antigen (HLA) genes were conflicting and inconclusive. In the present study, we investigate HLA genes (HLA-DRA, HLA-DRB1, HLA-DQA1 and HLA-DQB1) in RM couples with unknown etiology and normal couples. METHODS Blood samples from 143 RM couples and 150 control couples were analyzed, firstly to validate previously reported association studies and secondly to explore whether any novel alleles or haplotypes specific to Indian populations can be observed to be associated with RM. HLA typing was carried out by DNA sequencing. RESULTS Results suggest an association of the DQB1*03:03:02 allele with RM (odd ratio = 2.66; p(c) = 0.02; confidence interval = 1.47-4.84). Haplotypes of the DQA1 and DQB1 risk alleles also showed a significant association with RM, albeit not after Bonferroni correction for multiple comparisons. CONCLUSIONS HLA-DQB1 appears to have a strong involvement in the manifestation of RM in this population from South India. The current genetic analysis of RM and control couples not only highlights the genes exhibiting a strong etiological role but also reflects the protective nature of some HLA genes against RM. Nevertheless, most of these alleles/haplotypes were not those that are implicated in RM in other ethnic backgrounds, and hence require further validation in other populations of India, from different ethnic and/or geographic backgrounds.

Role of progesterone receptor polymorphisms in the recurrent spontaneous abortions: Indian case

Background We attempt to ascertain if the 3 linked single nucleotide polymorphisms (SNPs) of the Progesterone Receptor (PR) gene (exon 1: G 1031 C; S344T, exon 4: G 1978 T; L660V and exon 5: C 2310 T; H770H) and the PROGINS insertion in the intron G, between exons 7 and 8, are associated with Recurrent Spontaneous Abortion (RSA) in the Indian population. Methodology/Principal Findings A total of 143 women with RSA and 150 controls were sequenced for all the 8 exons looking for the above 3 linked SNPs of the PR gene earlier implicated in the RSA, as well as for any new SNPs that may be possibly found in the Indian population. PROGINS insertion was screened by electrophoresis. We did not find any new mutations, not observed earlier, in our population. Further, we did not find significant role of the *2 allele (representing the mutant allele at the three SNP loci) or the T2 allele (PROGINS insertion) in the manifestation of RSA. We also did not find an LD pattern between each of the 3 SNPs and the PROGINS insertion. Conclusions/Significance The results suggest that the PR gene mutations may not play any exclusive role in the manifestation of RSA, and instead, given significantly higher frequency of the *2 allele among the normal women, we surmise if it does not really confer a protective role among the Indian populations, albeit further studies are required in the heterogeneous populations of this region before making any conclusive statement.

Role of 14-bp insertion/deletion polymorphism in HLA-G among Indian women with recurrent spontaneous abortions

Human leukocyte antigen (HLA)-G is predominantly expressed on the extravillous cytotrophoblasts at the fetal-maternal interface. The 14-bp polymorphism in exon 8 is associated with HLA-G messenger ribonucleic acid (mRNA) stability and isoform alternative splicing patterns, thereby influencing the functionality of HLA-G in pregnancy. We analysed the 14-bp indel polymorphism in 143 recurrent spontaneous abortions (RSAs) and 150 control couples. We did not find any significant difference in the 14-bp insertion/deletion allele frequencies among the RSA and control couples. Analysis for increased sharing of the polymorphism in the RSA and the control couples also did not show any significant difference. However, we found an increase in the frequency of the 14-bp deletion homozygotes in the RSA women, which could lead to extremely high levels of soluble HLA-G (sHLA-G).

Mitochondrial DNA variations associated with recurrent pregnancy loss among Indian women.

Several genetic factors have been found to be associated with recurrent pregnancy loss (RPL). However, not many attempts have been made to associate the mitochondrial DNA (mtDNA) variations with RPL. Therefore, we have analyzed the complete mtDNA of 100 women with RPL and 12 aborted fetal tissues. Our analysis revealed a total of 681 variations, most of which were in NADH Dehydrogenase (ND) genes that encode mitochondrial enzyme Complex I. Presence of T4216C variation (ND1 gene) in 9% of the RPL women and several pathogenic, and novel mutations suggest the role of mtDNA variations in RPL.

Mitochondrial DNA variation and substructure among the tribal populations of Andhra Pradesh, India

We analyzed mtDNA HVR‐I variation among six tribal populations—Andh, Pardan, Gond, Naikpod, Kolam and Chenchu—from Andhra Pradesh. These tribes belong to the Dravidian and Indo‐European linguistic group. Except for Chenchu, the rest of the tribal samples were collected from two or more than two locations. The analysis of molecular variance (AMOVA) of the sequences yields a significant FST value (0.045), suggesting a fair degree of genetic differentiation among these tribes. When the tribal samples collected from different locations were considered as subpopulations in AMOVA, it is found that the variation among the subunits within the tribal groups is smaller than among the tribes. However, when Chenchu is removed from the analysis, the magnitude of within and between groups diversity becomes similar. In the multidimensional scaling plot based on FST distances the Chenchu is found to be the extreme outlier. Exclusion of Chenchu from AMOVA analysis and multidimensional scaling plot does not result in any specific pattern of population clustering. Mismatch distribution suggest that Chenchu might have undergone a bottleneck effect and does not show evidence of past demographic expansion as shown by the other five tribal groups. A comparison of AP tribes with some other caste and tribal populations of India suggests common maternal genetic heritage. Am. J. Hum. Biol., 2008.

Tuberculous peritonitis diagnosed with the help of 18 F-FDG PET/CT scan: 18 F-FDG PET/CT scan

we observed in this study. However, our study is limited in several aspects. First, the assessment results of self-reported frailty may be influenced by mis-perception of subjective health, cognitive dysfunction, and an impairment in communication ability accompanying advanced age. In addition, interrater variability is another theoretical concern, although we have minimized this possibility by meticulous training of nurse researchers before study initiation. Finally, low case number and the presence of other unmeasured confounding factors may limit the generalizability of our findings. In conclusion, the assessment of self-report frailty, a simple point-of-care instrument, in ESRD patients thus can aid in the identification of those at higher risk of developing dialysis access failure in the future.

Toxic epidermal necrolysis and acute kidney injury due to glyphosate ingestion

The literature, particularly from India, is scarce on the renal effects of glyphosate poisoning. Glyphosate causes toxicity not only after its ingestion but also after dermal exposure by inhalation route and on eye exposure. We present a patient report of glyphosate consumption which resulted in toxic epidermal necrolysis – the first report after glyphosate consumption and acute kidney injury.