RESUMO
Vitamin B12 is an important cofactor in one-carbon metabolism whose dysregulation is associated with various clinical conditions. Indians have a high prevalence of B12 deficiency but little is known about the genetic determinants of circulating B12 concentrations in Indians. We performed a genome-wide association study in 1001 healthy participants in the Pune Maternal Nutrition Study (PMNS), replication studies in 3418 individuals from other Indian cohorts and by meta-analysis identified new variants, rs3760775 (P = 1.2 × 10-23) and rs78060698 (P = 8.3 × 10-17) in FUT6 to be associated with circulating B12 concentrations. Although in-silico analysis replicated both variants in Europeans, differences in the effect allele frequency, effect size and the linkage disequilibrium structure of credible set variants with the reported variants suggest population-specific characteristics in this region. We replicated previously reported variants rs602662, rs601338 in FUT2, rs3760776, rs708686 in FUT6, rs34324219 in TCN1 (all P < 5 × 10-8), rs1131603 in TCN2 (P = 3.4 × 10-5), rs12780845 in CUBN (P = 3.0 × 10-3) and rs2270655 in MMAA (P = 2.0 × 10-3). Circulating B12 concentrations in the PMNS and Parthenon study showed a significant decline with increasing age (P < 0.001), however, the genetic contribution to B12 concentrations remained constant. Luciferase reporter and electrophoretic-mobility shift assay for the FUT6 variant rs78060698 using HepG2 cell line demonstrated strong allele-specific promoter and enhancer activity and differential binding of HNF4α, a key regulator of expression of various fucosyltransferases. Hence, the rs78060698 variant, through regulation of fucosylation may control intestinal host-microbial interaction which could influence B12 concentrations. Our results suggest that in addition to established genetic variants, population-specific variants are important in determining plasma B12 concentrations.
Assuntos
Fucosiltransferases/genética , Vitamina B 12/metabolismo , Adulto , Alelos , Povo Asiático/genética , Criança , Pré-Escolar , Feminino , Fucosiltransferases/metabolismo , Frequência do Gene/genética , Genética Populacional , Estudo de Associação Genômica Ampla , Humanos , Índia , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Regiões Promotoras Genéticas/genética , Vitamina B 12/sangue , População Branca/genéticaRESUMO
OBJECTIVE: The purpose of this study was to describe fetal size on sonography in a rural Indian population and compare it with those in European and urban Indian populations. Methods. Participants were from the Pune Maternal Nutrition Study of India. Fetal growth curves were constructed from serial ultrasound scans at approximately 18, 30, and 36 weeks' gestation in 653 singleton pregnancies. Measurements included femur length (FL), abdominal circumference (AC), biparietal diameter (BPD), and occipitofrontal diameter, from which head circumference (HC) was estimated. Measurements were compared with data from a large population-based study in France and a study of urban mothers in Vellore, south India. RESULTS: Fetal AC and BPD were smaller than the French reference at 18 weeks' gestation (-1.38 and -1.30 SD, respectively), whereas FL and HC were more comparable (-0.77 and -0.59 SD). The deficit remained similar at 36 weeks for AC (-0.97 SD), FL (-0.43 SD), and HC (-0.52 SD) and increased for BPD (-2.3 SD). Sonography at 18 weeks underestimated gestational age compared with the last menstrual period date by a median of -1.4 (interquartile range, -4.6, 1.8) days. The Pune fetuses were smaller, even at the first scan, than the urban Vellore sample. CONCLUSIONS: Fetal size was smaller in a rural Indian population than in European and urban Indian populations, even in mid pregnancy. The deficit varied for different fetal measurements; it was greatest for AC and BPD and least for FL and HC.
Assuntos
Antropometria/métodos , Tamanho Corporal/fisiologia , Desenvolvimento Fetal/fisiologia , População Rural/estatística & dados numéricos , Ultrassonografia Pré-Natal/métodos , Ultrassonografia Pré-Natal/estatística & dados numéricos , Estudos de Coortes , Europa (Continente)/epidemiologia , Feminino , Idade Gestacional , Humanos , Índia/epidemiologia , Masculino , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
CONTEXT: Associations between age at menarche and risk of type 2 diabetes and cardiovascular disease are well established in adults. But little is known about these risks in adolescents. AIM: To examine the association between age at menarche and anthropometric indicators, and also examine nutrition among the rural adolescent girls of KONKAN region. SETTING AND DESIGN: We investigated 1,071 school going adolescent girls who underwent holistic education and various clinical investigations as a part of community program. Age at menarche was recorded and anthropometric measurements were performed. Macronutrient intake was estimated by 24 h recall. STATISTICAL ANALYSIS USED: We used trend statistics and logistic regression to examine the association. RESULTS: A total of 813 girls had attained menarche. Mean age at menarche was 13.0 years. When compared with premenarchal girls anthropometric parameters were significantly higher in postmenarchal girls (P < 0.05 for all) and the prevalence of stunting and thinness was lower (P < 0.001 for both). There was a decreasing trend for weight (P < 0.001), BMI (P < 0.001), and waist circumference (P < 0.05) with increasing age of onset of menarche, and increasing trend for stunting and thinness (P < 0.001 for both). More than 65% of the girls were eating below the recommended daily allowance of calories, protein, and fat. Adolescents with late onset of menarche had increased likelihood of stunting (P < 0.01) and thinness (P < 0.001). CONCLUSIONS: Adolescent girls in the KONKAN region with late menarche are thin and stunted. There is an urgent need to improve nutritional status of adolescent girls from KONKAN as malnutrition can affect the onset of menarche.
RESUMO
Low plasma concentrations of vitamin B-12 are common in Indians, possibly due to low dietary intakes of animal-source foods. Whether malabsorption of the vitamin contributes to this has not been investigated. A rise in the plasma holotranscobalamin (holo-TC) concentration after a standard dose of oral vitamin B-12 has been proposed as a measure of gastrointestinal absorption in people with normal plasma vitamin B-12 concentrations. We studied 313 individuals (children and parents, 109 families) in the Pune Maternal Nutrition Study. They received 3 doses of 10 microg (n = 191) or 2 microg (n = 122) of cyanocobalamin at 6-h intervals. A rise in plasma holo-TC of > or =15% and >15 pmol/L above baseline was considered normal vitamin B-12 absorption. The baseline plasma vitamin B-12 concentration was <150 pmol/L in 48% of participants; holo-TC was <35 pmol/L in 98% and total homocysteine was high in 50% of participants (>10 micromol/L in children and >15 micromol/L in adults). In the 10 microg group, the plasma holo-TC concentration increased by 4.8-fold from (mean +/- SD) 9.3 +/- 7.0 pmol/L to 53.8 +/- 25.9 pmol/L and in the 2 microg group by 2.2-fold from 11.1 +/- 8.5 pmol/L to 35.7 +/- 19.3 pmol/L. Only 10% of the participants, mostly fathers, had an increase less than the suggested cut-points. Our results suggest that an increase in plasma holo-TC may be used to assess vitamin B-12 absorption in individuals with low vitamin B-12 status. Because malabsorption is unlikely to be a major reason for the low plasma vitamin B-12 concentrations in this population, increasing dietary vitamin B-12 should improve their status.
Assuntos
Absorção Intestinal , Transcobalaminas/metabolismo , Deficiência de Vitamina B 12/diagnóstico , Vitamina B 12/metabolismo , Adulto , Estatura , Peso Corporal , Doenças Cardiovasculares/epidemiologia , Criança , Diabetes Mellitus Tipo 2/epidemiologia , Pai , Feminino , Ácido Fólico/sangue , Hemoglobinas/metabolismo , Homocisteína/sangue , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Relações Mãe-Filho , Vitamina B 12/sangue , Vitamina B 12/farmacologia , Deficiência de Vitamina B 12/sangueRESUMO
BACKGROUND: India is undergoing rapid epidemiological and nutritional transition largely as a consequence of rapid urbanisation. We investigated conventional and novel cardiovascular risk factors in rural and urban Indian men and studied their association with markers of vascular damage. METHODS: We randomly selected and studied 149 rural, 142 urban slum residents and 150 urban middle class middle aged Indian men. We measured conventional (obesity, blood pressure, lipids, smoking habits) and novel (proinflammatory and prothrombotic factors) cardiovascular risk factors and markers of vascular damage (carotid intima media thickness (IMT), von Willebrand Factor (vWF), e-selectin). RESULTS: There was a progressive increase in most of the conventional cardiovascular (CV) risk factors from rural to slum to urban middle class men. Plasminogen activator inhibitor-1 (PAI-1), platelet count, total homocysteine and C-reactive protein showed similar patterns. Carotid IMT was similar in the three groups; vWF was highest in rural and e-selectin in slum men. Adjusting for location, age explained 17%, obesity 3% and conventional risk factors 1% of the variance in carotid IMT, whilst novel cardiovascular risk factors were without any significant impact. CONCLUSIONS: Urbanisation increases obesity related as well as prothrombotic and proinflammatory CV risk factors in Indian men, but appears not to impact on IMT.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etnologia , Espessura Intima-Media Carotídea , Estilo de Vida/etnologia , População Rural , População Urbana , Adulto , Biomarcadores/sangue , Espessura Intima-Media Carotídea/tendências , Humanos , Índia/etnologia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , População Rural/tendências , População Urbana/tendênciasRESUMO
We examined the differential associations of each parent's height and BMI with fetal growth, and examined the pattern of the associations through gestation. Data are from 557 term pregnancies in the Pune Maternal Nutrition Study. Size and conditional growth outcomes from 17 to 29 weeks to birth were derived from ultrasound and birth measures of head circumference, abdominal circumference, femur length and placental volume (at 17 weeks only). Parental height was positively associated with fetal head circumference and femur length. The associations with paternal height were detectible earlier in gestation (17-29 weeks) compared to the associations with maternal height. Fetuses of mothers with a higher BMI had a smaller mean head circumference at 17 weeks, but caught up to have larger head circumference at birth. Maternal but not paternal BMI, and paternal but not maternal height, were positively associated with placental volume. The opposing associations of placenta and fetal head growth with maternal BMI at 17 weeks could indicate prioritisation of early placental development, possibly as a strategy to facilitate growth in late gestation. This study has highlighted how the pattern of parental-fetal associations varies over gestation. Further follow-up will determine whether and how these variations in fetal/placental development relate to health in later life.
Assuntos
Estatura/fisiologia , Índice de Massa Corporal , Desenvolvimento Fetal/fisiologia , Pais , Adulto , Fatores Etários , Feminino , Fêmur/anatomia & histologia , Cabeça/anatomia & histologia , Humanos , Índia , Masculino , Placenta/anatomia & histologia , Gravidez , Análise de Regressão , Fatores Sexuais , UltrassonografiaRESUMO
OBJECTIVE: This study was undertaken to study the effect of parity on maternal and neonatal characteristics. STUDY DESIGN: Maternal anthropometry, diet, micronutrient status, biochemistry, and physical activity were measured during pregnancy and detailed neonatal size recorded in 770 pregnancies in rural Maharashtra, India. RESULTS: Increasing parity was associated with larger offspring birth weight, skinfold thicknesses, and abdominal circumference, but not head circumference and length. Compared with primiparous women, multiparous women were older, less adipose, and more physically active but had similar education, socioeconomic status, nutritional intake, and weight gain during pregnancy. They had lower circulating concentrations of hemoglobin, albumin, ferritin, glucose, and insulin and lower total leucocyte counts at 18 and 28 weeks' gestation. There was no difference in their husbands' body size. The relationship between maternal parity and neonatal weight and adiposity was significant independent of the difference in maternal characteristics. CONCLUSION: Increasing maternal parity predicts increasing adiposity in the newborn infant. This may result from maternal nutritional, cardiovascular, or immunologic factors.