Association of angiotensinogen gene SNPs and haplotypes with risk of hypertension in eastern Indian population.

BACKGROUND: Angiotensinogen (AGT) enzyme comprises a vital module of RAAS system that effectively controls the blood pressure and related cardiovascular functions. Ample association studies have reported the importance of AGT variants in cardiovascular and non-cardiovascular adversities. But lately, owing to the complexity of the many anomalies, the haplotype based examination of genetic variation that facilitates the identification of polymorphic sites which are located in the vicinity of the causative polymorphic site, gets greater appreciation. METHODS: In the present study, we have done genotype and haplotype analysis of AGT gene in reference to hypertension to confirm the association of the two in an Indian population. To accomplish this, we performed candidate SNPs analysis and construct possible haplotypes across the AGT promoter and gene region in 414 subjects (256 Hypertensive cases and 158 controls). RESULTS: We found four SNPs (rs11568020: A-152G and rs5050: A-20C in promoter; rs4762 and rs699 in exon2) and 3 haplotypes (H4, H7 and H8) that showed a stronger positive association with hypertension. The haplotype H2 was showing protective association with hypertension. CONCLUSION: The results of the present study confirmed and reestablished the role of AGT gene variants and their haplotypes in the causation of hypertension in Indian population and showed that haplotypes can provide stronger evidence of association.

Chronic energy deficiency in some low socio-economic populations from South India: relationships between body mass index, waist-hip ratio and conicity index.

This paper reports the prevalence of chronic energy deficiency (CED) based on body mass index (BMI) and its relation to other adiposity measures namely, waist-hip ratio (WHR) and conicity index (CI) in some low socio-economic groups from South India. Two ethnic groups from each area type, namely, tribal, rural and urban areas, are included and samples of 646 men and 670 women belonging to six groups are selected on a multistage basis. Based on the measurements, BMI, WHR and CI are calculated. A considerable proportion of populations studied here experience CED. A higher proportion of women than men show CED. The BMI and WHR are slightly higher among men and WHR exhibits significant intersex difference. The CI is in expected ranges and all ethnic groups differ from each other in all measurements and indices. Age is strongly correlated with WHR and CI, but not with BMI. Both WHR and CI are influenced by BMI. BMI and sex are found to be significant contributors to the variation in WHR, and ethnicity also added to the variation in CI. The present study also concludes that adult malnutrition (as indicated by BMI) is spread to a considerable extent in these populations of low socio-economic status. It appears that the ethnic differences occurring in several measurements/indices reflect the economic and social conditions.

Diversity and divergence among the tribal populations of India.

Tribal populations of the Indian subcontinent have been of longstanding interest to anthropologists and human geneticists. To investigate the relationship of Indian tribes to Indian castes and continental populations, we analyzed 45 unlinked autosomal STR loci in 9 tribal groups, 8 castes, and 18 populations from Africa, Europe and East Asia. South Indian tribal populations demonstrate low within-population heterozygosity (range: 0.54 - 0.69), while tribal populations sampled further north and east have higher heterozygosity (range: 0.69 - 0.74). Genetic distance estimates show that tribal Indians are more closely related to caste Indians than to other major groups. Between-tribe differentiation is high and exceeds that for eight sub-Saharan African populations (4.8% vs. 3.7%). Telugu-speaking populations are less differentiated than non-Telugu speakers (F(ST): 0.029 vs. 0.079), but geographic distance was not predictive of genetic affinity between tribes. South Indian tribes show significant population structure, and individuals can be clustered statistically into groups that correspond with their tribal affiliation. These results are consistent with high levels of genetic drift and isolation in Indian tribal populations, particularly those of South India, and they imply that these populations may be potential candidates for linkage disequilibrium and association mapping.

Blood pressure levels among cross-cultural populations of Visakhapatnam district, Andhra Pradesh, India.

BACKGROUND: Elevated blood pressure is a leading cause of morbidity and mortality throughout the world, as a major contributor to cardiovascular diseases. Blood pressure tends to vary cross-culturally and studies to address the influence of acculturization/modernization on blood pressure are limited from India, particularly from Andhra Pradesh. AIM: To provide information on blood pressure levels and variability across population groups from the State of Andhra Pradesh, India, and to examine the influence of acculturization/modernization on blood pressure levels. SUBJECTS AND METHODS: The blood pressure levels among 1316 individuals (646 men and 670 women) belonging to two tribal (Khondh and Valmiki) and two caste groups (Wadabalija and Settibalija) from rural and urban areas from Andhra Pradesh were collected. Analysis of covariance (ANCOVA) was used to examine the effect of age and sex, and population differences. RESULTS: The distribution of blood pressure showed significant variability among these population groups. Higher levels of blood pressure were noticed in an acculturizing tribe, the Valmiki, than among the Khondh, a traditional tribal population. The results indicate that age had significant effect on both systolic and diastolic blood pressure levels. Also, the systolic blood pressure was relatively more sensitive than diastolic blood pressure to the effect of age. The sex did not contribute significantly to the variability of blood pressure. CONCLUSIONS: The study revealed significant population differences in the variability of blood pressure, with higher levels among acculturizing tribal population than the non-acculturizing group. But no significant variation was noticed between rural and urban slum dwellers. Age had a significant effect on blood pressure levels.

Finger ridge count correlations among four tribes of Andhra Pradesh, India.

The present paper reports the distribution of finger ridge count correlations among four tribal populations from Andhra Pradesh, India viz., Dulia, Kotia, Manne Dora and Manzai Mali, and examines the intra and inter population variation. Higher correlations are recorded in left hands compared to right hands, but they are not significant. The homologous fingers exhibit a stronger correlation. In all the tribes, the correlations between right hand fingers are relatively higher among women when compared to men. Regarding inter population variation Dulia men differ significantly from the men of Manne Dora and the Manzai Mali tribes, and Kotia women also differ from the women of the Manne Dora significantly. The average correlation coefficient of the present populations is similar to other Indian populations reported earlier but lower than African and European populations.

Gene flow from the Indian subcontinent to Australia: evidence from the Y chromosome.

Phenotypic similarities between Australian Aboriginal People and some tribes of India were noted by T.H. Huxley during the voyage of the Rattlesnake (1846-1850). Anthropometric studies by Birdsell led to his suggestion that a migratory wave into Australia included populations with affinities to tribal Indians. Genetic evidence for an Indian contribution to the Australian gene pool is contradictory; most studies of autosomal markers have not supported this hypothesis (; and references therein). On the other hand, affinities between Australian Aboriginal People and southern Indians were suggested based on maternally inherited mitochondrial DNA. Here, we show additional DNA evidence in support of Huxley's hypothesis of an Indian-Australian connection using single-nucleotide polymorphisms (SNPs) and short tandem repeats (STRs) on the nonrecombining portion of the Y chromosome (NRY). Phylogenetic analyses of STR variation associated with a major Australian SNP lineage indicated tight clustering with southern Indian/Sri Lankan Y chromosomes. Estimates of the divergence time for these Indian and Australian chromosomes overlap with important changes in the archaeological and linguistic records in Australia. These results provide strong evidence for an influx of Y chromosomes from the Indian subcontinent to Australia that may have occurred during the Holocene.

Genetic evidence on the origins of Indian caste populations.

The origins and affinities of the approximately 1 billion people living on the subcontinent of India have long been contested. This is owing, in part, to the many different waves of immigrants that have influenced the genetic structure of India. In the most recent of these waves, Indo-European-speaking people from West Eurasia entered India from the Northwest and diffused throughout the subcontinent. They purportedly admixed with or displaced indigenous Dravidic-speaking populations. Subsequently they may have established the Hindu caste system and placed themselves primarily in castes of higher rank. To explore the impact of West Eurasians on contemporary Indian caste populations, we compared mtDNA (400 bp of hypervariable region 1 and 14 restriction site polymorphisms) and Y-chromosome (20 biallelic polymorphisms and 5 short tandem repeats) variation in approximately 265 males from eight castes of different rank to approximately 750 Africans, Asians, Europeans, and other Indians. For maternally inherited mtDNA, each caste is most similar to Asians. However, 20%-30% of Indian mtDNA haplotypes belong to West Eurasian haplogroups, and the frequency of these haplotypes is proportional to caste rank, the highest frequency of West Eurasian haplotypes being found in the upper castes. In contrast, for paternally inherited Y-chromosome variation each caste is more similar to Europeans than to Asians. Moreover, the affinity to Europeans is proportionate to caste rank, the upper castes being most similar to Europeans, particularly East Europeans. These findings are consistent with greater West Eurasian male admixture with castes of higher rank. Nevertheless, the mitochondrial genome and the Y chromosome each represents only a single haploid locus and is more susceptible to large stochastic variation, bottlenecks, and selective sweeps. Thus, to increase the power of our analysis, we assayed 40 independent, biparentally inherited autosomal loci (1 LINE-1 and 39 Alu elements) in all of the caste and continental populations (approximately 600 individuals). Analysis of these data demonstrated that the upper castes have a higher affinity to Europeans than to Asians, and the upper castes are significantly more similar to Europeans than are the lower castes. Collectively, all five datasets show a trend toward upper castes being more similar to Europeans, whereas lower castes are more similar to Asians. We conclude that Indian castes are most likely to be of proto-Asian origin with West Eurasian admixture resulting in rank-related and sex-specific differences in the genetic affinities of castes to Asians and Europeans.

Asymmetry of finger ridge counts among four tribal populations of Andhra Pradesh, India.

The asymmetry among the four tribal populations Dulia, Kotia, Manne Dora and Manzai Mali is reported. The mean directional asymmetry (MDA) and mean absolute asymmetry (MAA) were measured for homologous fingers. The asymmetry follows a decreasing trend in radio-ulnar direction with higher mean values in thumb and index finger. The individual variation is also higher in these fingers. Neither sexual nor population differences are consistent. Jantz's Square root of A2 (another measure to assess asymmetry) for total finger ridge count and absolute finger ridge count does not indicate any significant sexual or ethnic differences. The results suggest that the underlying mechanisms influencing the level of asymmetry may be similar for all groups, and that certain dermatoglyphic areas like the thumb are more vulnerable to developmental/environmental stress, that cause asymmetry at the developmental stage.

Mitochondrial DNA variation in Nicobarese Islanders.

The aboriginal populations living in the Nicobar Islands are hypothesized to be descendants of people who were part of early human dispersals into Southeast Asia. However, analyses of ethnographic histories, languages, morphometric data, and protein polymorphisms have not yet resolved which worldwide populations are most closely related to the Nicobarese. Thus, to explore the origins and affinities of the Nicobar Islanders, we analyzed mitochondrial DNA (mtDNA) hypervariable region 1 sequence data from 33 Nicobarese Islanders and compared their mtDNA haplotypes to those of neighboring East Asians, mainland and island Southeast Asians, Indians, Australian aborigines, Pacific Islanders, and Africans. Unique Nicobarese mtDNA haplotypes, including five Nicobarese mtDNA haplotypes linked to the COII/tRNA(Lys) 9-bp deletion, are most closely related to mtDNA haplotypes from mainland Southeast Asian Mon-Kmer-speaking populations (e.g., Cambodians). Thus, the dispersal of southern Chinese into mainland Southeast Asia may have included a westward expansion and colonization of the islands of the Andaman Sea.

Group- and sex-specific effects of age, body composition and pulse rate on blood pressure variability in some cross-cultural populations of Visakhapatnam District; South India.

BACKGROUND: Hypertension is becoming a major public health problem in developing countries. Blood pressure tends to vary cross-culturally and is influenced by various factors including age, body composition and pulse rate. This paper reports the influence of age, body composition and pulse rate on blood pressure variability. DESIGN: The data were collected from 1316 individuals (646 men and 670 women) belonging to two tribes (Khondh and Valmiki) inhabiting hilly tribal area and two castes (Wadabalija and Settibalija) from both rural and urban areas from Visakhapatnam district, Andhra Pradesh, India. RESULTS: There are considerable ethnic differences in blood pressure and body composition variables. Age contributes significantly to the variance in blood pressure in these populations. However the influence of age is less pronounced in Khondh, a primitive/unacculturized tribe, while age exerts a profound effect on blood pressure variability in Valmiki, an acculturizing tribe. Further, the effect of age is more pronounced on systolic than on diastolic pressure and it contributes more to the blood pressure of women than men. The subcutaneous fatness measures (sum of three trunk skin fold thicknesses and sum of three extremities skin fold thicknesses) are significant predictors of both systolic and diastolic blood pressure in Khondh, Valmiki and Wadabalija, while body mass index (BMI) is an important predictor of both systolic and diastolic blood pressure in Settibalija. Pulse rate is often found to influence blood pressure of women. CONCLUSION: The age-associated variability of blood pressure confirms the proposition that variability is high in adverse environment, when modernization/acculturization is taken to represent environmental adversity. Apart from the influence of age, body composition/adiposity contributes significantly to the blood pressure variability.

Genetic variability of blood and saliva antigens and serum proteins among subtribes of Mali from Andhra Pradesh, India.

The subtribes of Mali viz. Manzai Mali and Bod Mali of Andhra Pradesh, India, were screened for A1A2B0, Rhesus (CcDEe) and MN blood groups, ABH saliva secretion and plasma proteins, namely haptoglobin, transferrin, caeruloplasmin and albumin. The genetic differences between the two subtribes are marginal and not significant except for ABH saliva secretion and plasma haptoglobin. Our observations suggest that the isolation of these two subtribes cannot date long back.

Multiple origins of the mtDNA 9-bp deletion in populations of South India.

The origins and genetic affinities of the more than 500 tribal populations living in South Asia are widely disputed. This may reflect differential contributions that continental populations have made to tribal groups in South Asia. We assayed for the presence of the intergenic COII/tRNALys 9-bp deletion in human mtDNA in 646 individuals from 12 caste and 14 tribal populations of South India and compared them to individuals from Africa, Europe, and Asia. The 9-bp deletion is observed in four South Indian tribal populations, the Irula, Yanadi, Siddi, and Maria Gond, and in the Nicobarese. Length polymorphisms of the 9-bp motif are present in the Santal, Khonda Dora, and Jalari, all of whom live in a circumscribed region on the eastern Indian coast. Phylogenetic analyses of mtDNA control region sequence from individuals with the 9-bp deletion indicate that it has arisen independently in some Indian tribal populations. Other 9-bp deletion haplotypes are likely to be of Asian and African origin, implying multiple origins of the 9-bp deletion in South India. These results demonstrate varying genetic affinities of different South Indian tribes to continental populations and underscore the complex histories of the tribal populations living in South Asia.

Consanguinity and its relationship to differential fertility and mortality in the Kotia: a tribal population of Andhra Pradesh, India.

Data on patterns of marriage, differential fertility and mortality were collected from 211 Kotia women residing in Visakhapatnam district of Andhra Pradesh, India. Consanguineous marriages made up just over a quarter of the total, and of these, father's sister's daughter (FSD) were more common than mother's brother's daughter (MBD). The mean inbreeding coefficient for the sample (F) was 0.0172. Women in consanguineous marriages had a lower mean number of total conceptions, live births and living offspring (net fertility) than women in non-consanguineous marriages. Significant heterogeneity was found in the means of living offspring for FSD, MBD and non-consanguineous couples, but not for conceptions and live births.

Genetic diversity of PTC taste sensitivity among tribal and caste populations of Andhra Pradesh, India.

The present paper reports the variability of PTC taste sensitivity among eight endogamous tribal populations inhabiting the Eastern Ghats of North Coastal Andhra Pradesh. It was compared with the genetic diversity of PTC taste sensitivity among tribal and caste populations of Andhra Pradesh. The tribal and caste groups present a relatively high genetic diversity, of which a major proportion is due to genetic differences within populations rather than that between populations. Castes show a higher heterogeneity than tribes, the difference being significant. The high genetic diversity found among Andhra populations may be attributed to social stratification and the practice of strict endogamy.

Distribution of blood pressure and influence of subcutaneous fat on systolic and diastolic levels in a tribal population.

The distribution of arterial blood pressure levels and the influence of subcutaneous fat on blood pressure are investigated among Mall, an agricultural tribe of Andhra Pradesh. Majority of Mali people exhibit optimum levels of blood pressure. The incidence of stage 1 hypertension is moderate. The mean levels of blood pressure are relatively higher among women compared to men. The regression co-efficient values indicate a positive influence of triceps and subscapular skinfold thickness on both systolic and diastolic blood pressure among Manzai Mali. The results are discussed in the light of earlier studies.

mtDNA variation in caste populations of Andhra Pradesh, India.

Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p < 0.002). The effects of social structure on mtDNA variation are much greater than those on variation measured by traditional markers. Explanations for this discordance include (1) the higher resolving power of mtDNA, (2) sex-dependent gene flow, (3) differences in male and female effective population sizes, and (4) elements of the kinship structure. Thirty distinct haplotypes are found in Africans, 17 in Asians, and 13 in Europeans. Mean nucleotide diversity is 0.019, 0.014, 0.009, and 0.007 for Africans, Indians, Asians, and Europeans, respectively. These populations are highly structured geographically (GST = 0.15; p < 0.001). The caste populations of Andhra Pradesh cluster more often with Africans than with Asians or Europeans. This is suggestive of admixture with African populations.

Genetic structure of the Manne Dora, a tribal population of Andhra Pradesh.

The Manne Dora, a small tribe inhabiting the north coastal districts of Andhra Pradesh, South India, have been studied for 24 genetic markers, including blood groups, plasma proteins, and red cell enzymes. A genetic distance analysis was used to test whether this tribe was part of another tribe, the Konda Dora, and to clarify its divergence from other tribal populations of Andhra Pradesh. The dendrogram and principal components analysis reveal clustering of the tribal populations in close agreement with geographic distance. The study indicates that the Manne Dora may have been genetically part of the Konda Dora and separated only recently.

A new glucose-6-phosphate dehydrogenase variant, G6PD Orissa (44 Ala-->Gly), is the major polymorphic variant in tribal populations in India.

Deficiency of glucose-6-phosphate dehydrogenase (G6PD) is usually found at high frequencies in areas of the world where malaria has been endemic. The frequency and genetic basis of G6PD deficiency have been studied in Africa, around the Mediterranean, and in the Far East, but little such information is available about the situation in India. To determine the extent of heterogeneity of G6PD, we have studied several different Indian populations by screening for G6PD deficiency, followed by molecular analysis of deficient alleles. The frequency of G6PD deficiency varies between 3% and 15% in different tribal and urban groups. Remarkably, a previously unreported deficient variant, G6PD Orissa (44 Ala-->Gly), is responsible for most of the G6PD deficiency in tribal Indian populations but is not found in urban populations, where most of the G6PD deficiency is due to the G6PD Mediterranean (188 Ser-->Phe) variant. The KmNADP of G6PD Orissa is fivefold higher than that of the normal enzyme. This may be due to the fact that the alanine residue that is replaced by glycine is part of a putative coenzyme-binding site.