Host genetic factors including major histocompatibility complex (MHC) polymorphisms influence both susceptibility to leprosy per se and also to leprosy type. Non-MHC genes may play an important role, but such genes remain undefined. The influence of two non-MHC candidate genes was assessed in a case-control study of Bengali leprosy patients from Calcutta. Recent studies have implicated variation in the vitamin D receptor (VDR) gene in susceptibility to several diseases, including osteoporosis and pulmonary tuberculosis. In this population, homozygotes for the alternate alleles of the VDR polymorphism are associated, respectively, with lepromatous and tuberculoid leprosy. The NRAMP1 (natural resistance associated macrophage protein 1) gene may influence human mycobacterial disease susceptibility based on studies with the murine homologue Nramp1. However, no significant association was found between NRAMP1 and leprosy susceptibility. This study suggests that the VDR polymorphism may influence susceptibility to some diseases by affecting the type and the strength of the host immune response.
Skin pigmentation is one of the most variable phenotypic traits in humans. A non-synonymous substitution (rs1426654) in the third exon of SLC24A5 accounts for lighter skin in Europeans but not in East Asians. A previous genome-wide association study carried out in a heterogeneous sample of UK immigrants of South Asian descent suggested that this gene also contributes significantly to skin pigmentation variation among South Asians. In the present study, we have quantitatively assessed skin pigmentation for a largely homogeneous cohort of 1228 individuals from the Southern region of the Indian subcontinent. Our data confirm significant association of rs1426654 SNP with skin pigmentation, explaining about 27% of total phenotypic variation in the cohort studied. Our extensive survey of the polymorphism in 1573 individuals from 54 ethnic populations across the Indian subcontinent reveals wide presence of the derived-A allele, although the frequencies vary substantially among populations. We also show that the geospatial pattern of this allele is complex, but most importantly, reflects strong influence of language, geography and demographic history of the populations. Sequencing 11.74 kb of SLC24A5 in 95 individuals worldwide reveals that the rs1426654-A alleles in South Asian and West Eurasian populations are monophyletic and occur on the background of a common haplotype that is characterized by low genetic diversity. We date the coalescence of the light skin associated allele at 22–28 KYA. Both our sequence and genome-wide genotype data confirm that this gene has been a target for positive selection among Europeans. However, the latter also shows additional evidence of selection in populations of the Middle East, Central Asia, Pakistan and North India but not in South India.
A longitudinal study of 298 rural Bangladeshi infants found evidence of growth faltering starting at 3 months of age. Anthropometric status declined substantially in the first 2 years of life, with weight-for-height (WHZ) falling from 20·49 to 2 1·75, weight-for-age (WAZ) from 2 1·18 to 22·87 and height-for-age (HAZ) from 21·00 to 2 1·88. Higher concentrations of the acute-phase protein a-1-acid glycoprotein (AGP) and higher gut mucosal damage (as signified by raised lactulose:mannitol (L:M) ratios) were both associated with chronic malnutrition as indicated by poorer HAZ and WAZ scores (P¼ 0·011 and 0·005 for AGP and 0·039 and 0·019 for L:M ratio, respectively). Higher Hb levels were related to improved z-scores, while elevation of Giardia-specific IgM titre (GSIgM) was associated with poor WAZ and WHZ (P¼ 0·015 and 0·039, respectively). IgG did not show any significant association with z-scores and the L:M ratio did not correlate with any of the inflammation markers or Giardia infection. The prevalence of geohelminth infections was low (only 4 % in the total study period). However, the level of GSIgM indicated high endemicity of Giardia infection from early in life, although very few cysts were detected from stool samples. These findings suggest that rural Bangladeshi infants are being exposed to high levels of infection with concomitant gut damage and growth faltering. Infant growth: Intestinal permeability: Giardia intestinalis: Giardia-specific IgM antibody: a-1-Acid glycoproteinThe burden of undernutrition among most young Bangladeshi children remains very high and a recent nationwide study (1) found that 40·8 % of children under 5 years old were stunted, 47·1 % were underweight and 11·9 % were wasted. These high burdens reflect both shorter-and longer-term insults. Growth faltering which is common in many developing countries starts at an early age with weight-for-age z-scores (WAZ) and weight-for-height z-scores (WHZ) falling from about 3 months of age until about 12 months of age, whereas the decline in height-for-age z-score (HAZ) starts immediately and continues until about 24 months of age (2) . The time period between 3 and 24 months of age of a child has been described as 'the window of opportunity for addressing undernutrition' (2,3) and so interventions to improve nutritional status throughout the growth period must be accomplished within this rather short period of childhood.
SummaryWe conducted a randomized clinical intervention trial over 24 weeks on a tea estate in north-east Bangladesh to investigate the effect of iron supplementation and anthelmintic treatment on the labour productivity of adult female tea pluckers. A total of 553 full-time tea pluckers, not pregnant and not breastfeeding, were randomly assigned to one of the four intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and halfway through the trial (week 12), group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos. No signi®cant difference in labour productivity was found between the four intervention groups over the trial period. However, there was a negative association for all three worms (Ascaris lumbricoides, Trichuris trichiura and hookworms) between the intensity of helminth infections (eggs/g faeces) and all measures of labour productivity. Lower haemoglobin values and anaemia (< 120 g/l Hb) were both associated with lower labour productivity and more days sick and absent. Taller women with greater arm circumference were able to pluck more green leaves, earn higher wages and were absent less often.keyword Ascaris, Trichuris and hookworm infections, deworming, iron supplementation, tea pluckers, labour productivity correspondence
Genetically determined differences in immune responses to environmental agents may underlie susceptibility to many autoimmune and infectious diseases. Leprosy provides an example of a polarity in the type of immune response made to an infectious agent, and there is evidence that the major histocompatibility complex is genetically linked to leprosy type. It was found that HLA-DR2 is associated with both tuberculoid and lepromatous types of leprosy; however, a variant at position -308 of the promoter of the neighboring tumor necrosis factor (TNF) gene was increased in frequency in lepromatous (odds ratio = 3.0, P = .02) but not tuberculoid leprosy. Some studies have found higher serum levels of TNF in lepromatous than tuberculoid leprosy, and high TNF levels are found in malaria and leishmaniasis, which are also associated with this TNF allele. It is speculated that this association reflects genetic variability in cytokine production, which influences the immune response to and clinical outcome of leprosy.
A similar pattern of spousal association for IQ scores and personality traits was found in two British samples from Oxford and Cambridge. There was no indirect evidence from either sample to suggest that convergence occurred during marriage. All observed assortative mating might well be due to initial assortment.
An adapted 'sense of coherence' scale short form (SOC-13) was administered in nine languages of Eritrea with a total of 265 participants (162 women and 103 men) in order to assess 'resilience' in quantitative terms. Statistical analysis yielded significant differences in SOC scores between the displaced and non-displaced: mean=54.84 (SD=6.48) in internally displaced person (IDP) camps, compared with mean=48.94 (SD=11.99) in urban and rural settlements (t=3.831, p<0.001). Post-hoc tests revealed that the main difference is between IDP camp dwellers and urban (non-displaced) residents. Those in rural but traditionally mobile (pastoralist or transhumant) communities scored more or less the same as the urban non-displaced - i.e. significantly higher than those in IDP camps (p<0.05). Analysis of variance showed that displacement has a significantly negative effect on women compared with men (RR=0.262, p<0.001). Repeating the analysis for the three groups confirmed that urban and pastoralist/transhumant groups are similar, while women in IDP camps are lower scoring (RR=0.268, p<0.001), Hamboka women being worst affected due to their experience of serial displacement. These findings are interpreted and discussed in the light of qualitative information gleaned from the study participants' interrogation of the content of the SOC scale; and in the wider context of historical, socio-political and cultural characteristics of Eritrea. The study's implications for humanitarian and public health policy are considered.
Use of BMI as a surrogate for body fat percentage is debatable and universal BMI cut-off points do not seem appropriate; lower cut-off points than currently recommended by WHO should be used in some populations, especially in Asia. The adult WHO BMI database indicates that, on average, women are more obese than men, while men are more likely to be pre-obese than women. Urban rates of overweight and obesity are generally higher than rural rates in both sexes. The trend in pre-obesity and obesity over time is generally upward, with very marked increases in the USA and UK in both sexes over the last 10 years.
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