Kallur Nava Saraswathy

Spectrum of MTHFR gene SNPs C677T and A1298C: a study among 23 population groups of India.

Elevated homocysteine is a risk factor for many complex disorders. The role of methylenetetrahydrofolate reductase (MTHFR) gene in methylation of homocysteine makes it one of the most important candidate genes for these disorders. Considering the heterogeneity in its distribution in world populations, we screened MTHFR C677T and A1298C single nucleotide polymorphisms in a total of 23 Indian caste, tribal and religious population groups from five geographical regions of India and belonging to four major linguistic groups. The frequencies of MTHFR 677T and 1298C alleles were found to be 10.08 and 20.66%, respectively. MTHFR homozygous genotype 677TT was absent in eight population groups and homozygous 1298CC was absent in two population groups. 677T allele was found to be highest among north Indian populations with Indo-European tongue and 1298C was high among Dravidian-speaking tribes of east India and south India. The less common mutant haplotype 677T-1298C was observed among seven population groups and overall the frequency of this haplotype was 0.008, which is similar to that of African populations. cis configuration of 677T and 1298C was 0.94%. However, we could not find any individual with four mutant alleles which supports the earlier observation that presence of more than two mutant alleles may decrease the viability of foetus and possibly be a selective disadvantage in the population.

Population Severance in Manipur at Dopamine Receptor D2 Locus

INTRODUCTIONnTibeto-Burman language-speaking Mongoloid groups of northeast India are reported to be genetically highly heterogeneous. Manipur, one of the states of this region sharing a major International border with Myanmar, is also expected to be diversified as seen by its large number of tribal and nontribal groups. A number of genomic markers, that is, autosomal, mitochondrial, and Y chromosomal ones, have been used to understand the peopling of the northeast region.nnnAIMSnIn this article, an attempt is made to understand the peopling of Manipur using three sites (Taq1A, Taq1B, and Taq1D) on the dopamine receptor D2 (DRD2) gene through allele and haplotype frequencies and their distribution patterns.nnnMETHODSnIn total, 367 blood samples were collected from eight populations of which three (Meitei, Muslims, and Bamon) are nontribal groups and five (Aimol, Kabui, Paite, Kom, and Thadou) are tribal groups.nnnRESULTSnAll the three sites are polymorphic in all the studied populations with relatively lower heterozyosities indicating a genetic discontinuity between the populations of mainland India and northeast India, suggesting the unlikeliness of eastward migration of people from Africa through India.nnnCONCLUSIONnHigh heterogeneity and predominance of ancestral haplotype (B2D2A1) among the Meitei suggest an admixture of incoming mongoloid groups with an already existing protoastroloid element. The study also highlights the distinctiveness of Manipuri population groups with respect to DRD2 gene polymorphism.

A Genomic Insight into the Peopling of Manipur, India

INTRODUCTIONnmanipur, one of the northeastern states of India, lies on the ancient silk route and serves as a meeting point between the Southeast Asia and South Asia.nnnAIMSnthis study was conducted to understand and estimate the genomic diversity among various population groups of Manipur, with a major goal of getting an insight into the peopling of India.nnnMETHODSnseven human-specific Alu insertion/deletion polymorphisms were screened on 366 individuals belonging to eight ethnic groups of Manipur, including both tribal (Aimol, Kabui, Kom, Paite, and Thadou) and nontribal populations (Bamon, Muslims, and Meitei).nnnRESULTSnall the biallelic loci are polymorphic except CD4, which is monomorphic in six out of the eight studied populations. The average heterozygosity values are low (0.309-0.395), with relatively higher average heterozygosity values among Bamons and Muslims than other studied populations, suggesting admixture in these two populations. Lower heterozygosity values of the tribal populations place them closer to the Chinese and Southeast Asian populations, indicating their late arrival in India coupled with geographical isolation.nnnCONCLUSIONnthis study provides evidence for the genetic heterogeneity of the Manipur populations. It also supports the hypothesis, based on the archeological and linguistic findings, that the northeastern populations of India have a close genetic affinity with the southeastern and East Asian populations. The genetic discontinuity observed between the studied populations and the other non-Northeast Indian populations suggests the role of northeast border as a barrier rather than a corridor.

Isonymy and repeated pairs of surnames among the Muslims of Manipur, India.

Surnames have been used for studying population structure in different parts of the globe. The present study is aimed at indirectly estimating the degree of inbreeding from surnames and understanding the influences of the clan-like structure on mate selection among Manipuri Muslims. The proportion of isonymy I was found to be 0.0144. The non-random and random components were -0.0226 and 0.0239, respectively. The total inbreeding coefficient was estimated to be 0.0018. The scores of random pairs (RP) and random repeated pairs (RPr) were 0.026 and 0.010, respectively. The score of RP was higher than the RPr which gives a ratio of 0.38, indicating that Manipuri Muslims have a tendency of acquiring mates from within a given set of surnames while not in favour of isonymy. To conclude, surname/clan is a criterion for mate selection for various reasons among this population.

Genetic thromobophilia in pregnancy: a case–control study among North Indian women

In the present study, an attempt is made to understand the role of genetic thrombophilias i.e. MTHFR C677T and FVL in the causation of various pregnancy complications like pregnancy induced hypertension (PIH), recurrent abortions, intra-uterine growth retardation (IUGR) and intra-uterine death on the whole and also individually along with the comparative assessment of pathophysiological basis of various pregnancy complications via the genetic proximities. One thousand and eleven (1,011) women of reproductive age group were recruited in the present study comprising various complications and controls. Recruitment criteria for all the pregnancy complications and controls was made and followed strictly. MTHFR C677T and FVL mutation detection was done in all the subjects. Vegetarianism was found to be significant risk factors for all the pregnancy complications and also when assessed individually. With respect to MTHFR C677T polymorphism, higher frequency of 677T allele was found among controls as compared to cases. 677T allele was found to pose decreased risk for various pregnancy complications on the whole and also individually. On adjusting the diet, regression analysis revealed no risk of mutant allele (T) for various pregnancy complications. FVL homozygous mutants were found to be absent among controls. In conclusion, the present study depicts dietary pattern as one of the most important factors in demonstrating the role of MTHFR C677T in various pregnancy complications and is indicative of a relatively deleterious effect of double dose of FVL in the presently studied population. Additionally, these polymorphisms play an important role in the orchestration of PIH to IUGR and vice versa.

MTHFR C677T Polymorphism Among Three Mendelian Populations: A Study from North India

The conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate is catalyzed by 5,10-methylenetetrahydrofolate reductase (MTHFR) using NADPH as a reducing agent. MTHFR variant genotypes may confer elevated plasma homocysteine levels, a condition known as hyperhomocysteinemia (Yamada et al. 2001), also consistent with a decline in remethylation of homocysteine to methionine (Rosenblatt and Fenton 2001). Hyperhomocysteinemia, or mild elevation of blood homocysteine, is an established risk factor for cardiovascular disease (Varga et al. 2005) and is associated with increased mortality in patients with confirmed coronary artery disease. Hyperhomocysteinemia is also linked to an increased incidence of neural tube defects (Vander Put et al. 1997). The MTHFR converts dUMP to dTMP, a limiting nucleotide for DNA synthesis, whereas the latter is required to produce methionine for DNA methylation (Blount et al. 1997). The MTHFR gene is polymorphic, with single-nucleotide variants within codon 677 in exon 4 (C?T, ala to val; Frosst et al. 1995) and codon 1298 in exon 7 (A?C, glu to ala; Vander Put et al. 1998). The codon 677 variant encodes a thermolabile enzyme with reduced activity that leads to reduced plasma folate levels (Lalouschek et al. 2000). Many studies have indicated that these two mutations are associated with susceptibility to cardiovascular diseases (Cortese and Motti 2001), cerebrovascular diseases (Ranjith et al. 2003), neural tube defects (Vander Put et al. 1997), fetal loss, acute lymphoblastic leukemia (Ongaro and Scapoli 2004), colorectal cancer (Chen et al. 1996), thrombosis (Brattstrom et al. 1998), and a variety of other diseases.

An assessment study of CVD related risk factors in a tribal population of India

BackgroundNon communicable diseases (NCDs) have become a major concern for global health. Cardiovascular diseases (CVDs) contribute 48xa0% towards the deaths due to NCDs in India. Though studies have been conducted in urban and rural areas, data related to tribal communities is limited. The present study aims to examine various CVD related risk factors including hypertension, elevated fasting blood glucose, obesity and metabolic syndrome among a tribal population.MethodsThe present study was an observational, cross- sectional study conducted on Rang Bhotias, a tribal population of India. The participants were adults of age between 20 and 60xa0years. Prior to blood sample collection, interview schedule was administered which included relevant information like age, lifestyle, socio-economic status, education and occupation In addition to this, various anthropometric and physiological measurements were taken. Logistic regression was used to examine the association of the various health disorders related to CVDs with age, gender and behavioural factors (smoking, alcohol consumption and physical activity).ResultsA total of 288 participants were surveyed for the study including 104 males and 184 females. High BMI (56.6xa0%), hypertension (43.4xa0%), metabolic syndrome (39.2xa0%) and abdominal obesity (33.7xa0%) were the most prevalent CVD risk factors observed in the population. The multivariate logistic regression analysis, conducted to examine the contribution of risk factors including behavioural risk factors on the studied abnormalities, revealed age to be a significant risk factor for all the abnormalities except elevated fasting blood glucose. Gender and physical inactivity contributed significantly towards development of hypertension. Physical inactivity was also found to be associated with high BMI levels.ConclusionIn the present study, hypertension, high BMI levels, MS and abdominal obesity have been found to be high among the studied population. The status of the population with respect to these abnormalities implicates susceptibility of the community towards various common disorders. The prevention and treatment intervention programs should be implemented taking into consideration age and gender.

Distribution of beta-globin haplotypes among the tribes of southern Gujarat, India

The present study was carried out in Indo-European speaking tribal population groups of southern Gujarat (India) to elucidate the allelic and haplotypic content of β-globin system in individuals with HbAA genotypes. 6 neutral restriction sites of the β-globin system were analysed and various statistical parameters were estimated to draw meaningful interpretations. All the 6 sites were found to be polymorphic and most were in Hardy-Weinberg Equilibrium in the studied group. Haplotypes were constructed using two different combinations of the 6 restriction sites analysed. Analysis of the 5 sites revealed a set of three predominant haplotypes, +----, -++-+ and -+-++; and haplotypes +--, ++- and +++ were found to be the most frequent when the 3 sites were used to construct the haplotypes. Haplotypic heterozygosity levels (>83%) observed in the present study group were comparable to those observed in African and Afro-American populations and greater than other world populations. All the ancestral haplotypes, +-----, -++-+, -+-++ and ----+ were found in the study group. The distribution pattern of various haplotypes was consistent with the global pattern. The paucity of comparable data from other Indian populations restricted one from making interpretations about the study groups relationships with other Indian populations but the results were indicative of older population histories or experience of gene flow by the study group and their affinities with populations of southern India.

Opportunity for natural selection among five population groups of Manipur, North East India.

Opportunity for natural selection among five population groups of Manipur in comparison with other North East Indian population has been studied. Crows index as well as Johnston and Kensingers index for natural selection were calculated based on differential fertility and mortality. The mortality component was found to be lower compared to fertility component in all the populations which may attribute to comparatively improved and easily accessible health care facilities. However, different selection pressures, artificial and natural, seem to be influencing the selection intensity through induced abortion and spontaneous abortion among the two non-tribal migrant groups: Bamon and Muslims, respectively. This study highlights the probable interaction of artificial and natural selection in determining the evolutionary fate of any population group.

Haptoglobin polymorphism among fourteen populations of India.

Haptoglobin (HP) is a serum protein that has the capability of binding the extracorpuscular haemoglobin released during haemolysis. It plays an important role in protection of haemolytic disease by reducing the oxidative and peroxidative potential at free haemoglobin. The present study was aimed to determine the prevalence of HP polymorphism among different Indian populations, anthropologically belonging to diverse ethnicity. The polymorphism was screened among 642 unrelated individuals belonging to 14 population groups of India including both tribal and non-tribal caste groups from different geographical regions of India with distinct linguistic affiliations. An attempt is also made to understand the distribution of HP polymorphism among the studied populations. The result reveals the HP gene to be polymorphic in all the studied populations. Except the two tribal populations (Thotis of Andhra Pradesh and Patelias of Rajasthan) and one caste population (Rajput of Himachal Pradesh), all the studied populations are found to obey the Hardy-Weinberg equilibrium. The significance of the present study is elucidated with the prevalence of high mutant HP*2 allele frequency in India. Selection could be one of the most plausible explanations for this high HP frequency because of its uniformly high occurrence among all the studied populations.