Maternal one carbon metabolism and interleukin-10 &-17 synergistically influence the mode of delivery in women with Early Onset Pre-Eclampsia.

OBJECTIVE: Studies on One Carbon Metabolism (OCM), Interleukins-10 &-17 (IL-10/-17) & ßhCG in pre-eclampsia and its delivery outcome (preterm birth) reveal contradictory results, attributed to clinical heterogeneity (early/late onset pre-eclampsia) or preterm/term birth. Disturbed OCM also influences IL-10 &-17 during pregnancy. We sought to investigate the synergism between OCM and IL-10/-17 mediated immune-regulation through ßhCG in Early onset pre-eclampsia (EO-PE) patients, delivering preterm, among North Indian women. STUDY DESIGN: Case-control study with a total of 399 pregnant women (EO-PE delivering preterm = 199; Normotensives delivering at term = 200). Maternal genotypes & biochemical estimations along with fetal genotypes on subset (n = 72) pertaining to OCM and IL-10/-17 regulation were assessed. MAIN OUTCOME MEASURES: Association of 1) maternal plasma levels with EO-PE 2) maternal and fetal genotypes with EO-PE. 3) Effect of Hyper-homocysteinemia (surrogate of disturbed OCM) on differential immune regulation (IL10,-17, ßhCG) in EO-PE and mode of delivery. RESULTS: Hyper-homocysteinemia posed an increased risk of three folds for EO-PE. Both, folate and B12 deficiencies were associated with elevated homocysteine in EO-PE. Further, MTHFR 677TT homozygotes was present only in EO-PE indicating its detrimental role. However, maternal IL17-197AA genotype showed decreased risk for EO-PE. Furthermore, elevated maternal plasma IL-17 along with elevated IL-10 & ßhCG were observed in EO-PE. Taken together, altered homocysteine metabolism was associated with high IL10 in EO-PE; and was more pronounced in spontaneous vaginal deliveries as compared to induced/caesarean section deliveries. CONCLUSIONS: We report homocysteine mediated IL-10 &17 dysregulation and its influence on mode of delivery in EO-PE, possibly through initiation of cervical ripening. Further, these could serve potential biomarkers of EO-PE & its delivery outcome among vulnerable populations with similar nutritional & genetic predispositions.

Diversified genomic contribution among south Indian populations--a study on four endogamous groups of Andhra Pradesh.

BACKGROUND: The present study examines genomic variation among three tribal (Nayakpod, Thoti and Kolam) and a caste (Niyogi Brahmin) population groups of Andhra Pradesh, south India. AIM: The present study examined the genomic diversity of the populations in relation to other population groups of India using 20 autosomal loci. SUBJECTS AND METHODS: A total of 204 blood samples from the population groups described above were collected and analysis was carried out following standard protocols. RESULTS: All markers were found to be polymorphic in these groups except AluCD4 among Thotis. High average heterozygosity values (0.3927 among Thotis to 0.4268 among Brahmins) are comparable with the available autosomal (Alu and restriction site polymorphisms) data for the Nilgiri hill tribes of Tamil Nadu, south India. The gene differentiation value (Gst) was found to be 4.2. The principal coordinate analysis (PCO) based on data from the 20 markers presents a smaller cluster of presently studied populations than that of the Nilgiri hill tribes of Tamil Nadu, south India. CONCLUSION: Although the presently studied populations of Andhra Pradesh have heterozygosity similar to that of Nilgiri hill populations, the former are more closely placed on the PCO plot than the latter, who are more scattered. Also the gene differentiation (Gst) of the former is much lower than that of the latter, indicating considerable regional variation in the inflow of genes from diverse ethnic groups within south India.

Folic acid, dietary habits, and homocysteine levels in relation to neural tube defects: A case-control study in North India.

PURPOSE: The present study attempts to understand the complex contribution of biochemical (plasma homocysteine) and nutritional parameters (dietary pattern and folate supplementation) to the neural tube defects (NTDs) affected pregnancies and controls in North Indian population. METHODS: Case-control study design was adopted to assess the role of folic acid, dietary habits, and homocysteine in relation to NTD births. The subjects comprised of 130 mothers of affected children (cases) and 233 mothers of healthy children (controls), who were either carrying NTD fetus or gave birth to NTD child. RESULTS: The mean homocysteine levels were elevated in cases (15.71 ± 8.35 µmol/L) as compared to controls (12.87 ± 5.95 µmol/L) but were lower among the non-vergetarians (13.55 ± 6.64 µmol/L) than the vegetarians (14.78 ± 7.93 µmol/L). Vegetarian dietary habit increased the NTD risk by 1.6 fold (95% CI = 1.0-2.7) while folic acid supplementation demonstrated a protective effect for conceptions (OR = 0.59; 95% CI = 0.3-0.9). Consumption of folic acid with non-vegetarian diet witnessed lowering of homocysteine in cases (12.88 ± 6.81 µmol/L) and in controls (11.85 ± 5.54 µmol/L), with an odds ratio depicting a 3.1 fold risk for consuming vegetarian diet without folic acid supplementation during the peri-conceptional period. CONCLUSION: It is suggested that plasma hyperhomocysteinemia bears negative impact on child-bearing women group, of north Indian ancestry, in modulating the risk of NTDs. Efforts should be made to enhance awareness regarding folic acid and vitamin B12 (non-vegetarian diet) supplementations alongwith proper nutritional intake among women, especially those consuming vegetarian diet to control homocysteine levels in order to reduce the risk of NTDs.