Has the long-predicted decline in consanguineous marriage in India occurred?

To an extent the question posed in the title of this paper can simply be answered in the affirmative. Based on the extensive data available from the National Family Health Survey-1 (NFHS-1) conducted in 1992-93 and NFHS-4 in 2015-16 there has been a significant overall decline of some 19% in the prevalence of consanguineous marriage in India. However, when examined at state level the picture is more complex, with large reductions in consanguinity in southern states where intra-familial marriage previously has been strongly favoured, whereas in some northern states in which close kin unions traditionally have been proscribed small increases were recorded. In a country such as India, comprising an estimated 18% of the current world population and with multiple ethnic, religious, geographical and social sub-divisions, apparently contrary findings of this nature are not unexpected - especially given the major shifts that are underway in family sizes, in education and employment, and with rapid urbanization. The changing health profile of the population also is an important factor, with non-communicable diseases now responsible for a majority of morbidity and premature mortality in adulthood. The degree to which future alterations in the prevalence and profile of consanguineous marriage occur, and at what rate, is difficult to predict - the more so given the markedly diverse cultural identities that remain extant across the Sub-Continent, and ongoing intra-community endogamy.

iNOS polymorphism modulates iNOS/NO expression via impaired antioxidant and ROS content in P. vivax and P. falciparum infection.

Nitric oxide (NO) has dicotomic influence on modulating host-parasite interplay, synchronizing physiological orchestrations and diagnostic potential; instigated us to investigate the plausible association and genetic regulation among NO level, components of oxidative stress, iNOS polymorphisms and risk of malaria. Here, we experimentally elucidate that iNOS promoter polymorphisms are associated with risk of malaria; employing mutation specific genotyping, functional interplay using western blot and RT-PCR, quantitative estimation of NO, total antioxidant content (TAC) and reactive oxygen species (ROS). Genotyping revealed significantly associated risk of P. vivax (adjusted OR = 1.92 and 1.72) and P. falciparum (adjusted OR = 1.68 and 1.75) infection with SNP at iNOS-954G/C and iNOS-1173C/T positions, respectively; though vivax showed higher risk of infection. Intriguingly, mutation and infection specific differential upregulation of iNOS expression/NO level was observed and found to be significantly associated with mutant genotypes. Moreover, P. vivax showed pronounced iNOS protein (2.4 fold) and mRNA (2.5 fold) expression relative to healthy subjects. Furthermore, TAC and ROS were significantly decreased in infection; and differentially decreased in mutant genotypes. Our findings endorse polymorphic regulation of iNOS expression, altered oxidant-antioxidant components and evidences of risk association as the hallmark of malaria pathogenesis. iNOS/NO may serve as potential diagnostic marker in assessing clinical malaria.

Role of IL-1ß, IL-6 and TNF-α cytokines and TNF-α promoter variability in Plasmodium vivax infection during pregnancy in endemic population of Jharkhand, India.

BACKGROUND: The combinatorial effects of Plasmodium infection, perturbation of inflammatory responses and the dichotomic role of TNF promoter polymorphism has potential clinical and physiological relevance during pregnancy. OBJECTIVE AND METHODS: This coordinated orchestration instigated us to investigate the circulating level of inflammatory cytokines (IL-1ß, TNF-α and IL-6) employing ELISA in a stratified group of samples and the plausible genetic association of TNF-α -308 G/A using PCR-RFLP/sequencing during Plasmodium vivax infection in pregnancy. RESULTS: We observed significantly elevated concentrations of IL-1ß were observed, followed by IL-6 and TNF-α in women with malaria (WWM) and in malaria in pregnancy (MIP). Further, elevated IL-1ß, followed by TNF-α and IL-6 were detected in the non-infected pregnancy group. The differential dynamics of inflammatory cytokine concentration during each trimester of pregnancy with and without P. vivax infection were detected. For the first time, a high level of IL-6 was observed in the first trimester of MIP and high IL-1ß in healthy pregnancies. In the second trimester, however, we observed a high level of IL-1ß in the MIP group compared to a sustained high level of IL-1ß in the healthy pregnancy group. In the third trimester, high IL-1ß was sustained in the MIP group and healthy pregnancies acquired a high TNF-α level. The genotypic distribution for the TNF-α promoter -308 G/A position was observed to be nonsignificant and mildly associated during MIP (OR = 1.4) and in WWM (OR = 1.2). Moreover, based on genotypic distribution, we observed a well-correlated and significantly elevated TNF-α concentration in the mutant homozygote genotype (AA; p = 0.001) followed by heterozygotes (GA; p = 0.0001) and ancestral genotypes (GG; p = 0.0001) in both MIP and WWM subjects. CONCLUSION: The observation of elevated IL-1ß and IL-6 in MIP and TNF-α in WWM may be regarded as a prognostic inflammatory marker of infection and pregnancy. Most particularly, the TNF-α concentration and its polymorphic variability in the promoter region may indicate genetic susceptibility and mildly influence the risk for P. vivax infection during pregnancy and in women with malaria.