Index Introduction Materials and Methods Results Discussion Acknowledgment References

Introduction

Of the several abnormal haemoglobins identified to date, three variants—haemoglobin S (HBS), haemoglobin E (HBE), and haemoglobin D (HBD), in varying proportions—are predominantly prevalent in India. The cumulative allele frequency in different parts of India for these variants is 5.35% (Balgir, 1996). The carrier frequency of haemoglobinopathies varies from 3% to 17% in different population groups of India (Balgir, 2000). Thus, haemoglobinopathies are a huge genetic burden and pose a major healthcare challenge in India.

Several lines of evidence, including plausible cellular mechanisms, confirm that sickle cell trait provides up to 90% protection against death due to malaria (Hill et al., 1991). There is also good clinical evidence that two of the commonest disorders, HBS and alpha (+)/thalassaemia trait, also afford protection against malaria (Flint et al., 1998; Pasvol, 2006).

Glucose-6-phosphate dehydrogenase (G6PD) is one of the key enzymes of the hexose-monophosphate shunt pathway, the deficiency of which is an X-linked recessive trait. The frequency of G6PD*def in India varies from complete absence among the Ganchha of Rajasthan (Choubisa, 1985) to 0.271 among the Nagas of Nagaland (Bhasin, 2006).

Materials and Methods

Manipur has a population of 2.388 million. According to the latest available census report of India, the total population of Meitei, Pangan (Manipuri Muslim), and the Kabui (tribal) are 1361521, 167204, and 62216, respectively (Census of India, 2001). Bamons (Manipuri Brahmins) constitute 5% of the total Meitei population of Manipur.

Pangans are a Caucasoid group in contrast to the neighbouring Mongoloid groups (Shah, 1990). They are present throughout Manipur and practise consanguineous marriages.

Ethnohistorically, the Bamon settlers represent the easternmost part of the so-called Caucasoid types but due to their intermarriage with Meitei women (Mongoloid group) over a long period of time, they now show both Caucasoid and Mongoloid features (Chakraborty et al., 1987). They inhabit the four valley districts of Manipur, namely Imphal East, Imphal West, Thoubal, and Bishnupur.

The Kabui is one of the endogamous tribes of Manipur and have long been living in different parts of north eastern India, especially Assam, Nagaland, and Manipur. The Kabui are a group of southern Mongoloids who migrated from southwest China to Myanmar and islands of Southeast Asia, and then made a northward movement back to Manipur (Kamei, 2004).

In the present study an attempt is made to estimate the frequencies of haemoglobinopathies in general and G6PD deficiency among the three population groups, i.e. Pangan, Bamon, and Kabui of Manipur, India (Figure 1).

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Figure 1. Map of Manipur showing Field site.

A total of 713 blood samples of either sex from three different population groups (302 Pangan, 300 Bamon, and 111 Kabui) of Imphal East, Imphal West, and Thoubal districts of Manipur, were collected by finger prick in EDTA (0.5 M)-coated Eppendorf tubes after obtaining prior written consent. All the blood samples were screened for haemoglobinopathies by using the Naked Eye Single Tube Red Cell Osmotic Fragility Test (NESTROFT) (Thomas et al., 1996). Of the 713 samples, 314 male samples (136 Pangan, 127 Bamon, and 51 Kabui) were also screened for G6PD deficiency by the Fluorescent Spot Test (Beutler and Mitchell, 1968).

Results

Among the three populations studied, the Kabui showed the highest frequency of both NESTROFT-positive (13.51%) and NESTROFT-doubtful cases (24.32%). The lowest frequencies of NESTROFT-positive (3.31%) and NESTROFT-doubtful (1.32%) individuals were found among the Pangans. Intermediate frequencies of NESTROFT-positive (10%) and NESTROFT-doubtful (11%) cases were found among the Bamons (Table 1). However, an opposite pattern of distribution is observed with respect to G6PD deficiency, i.e. it is the highest among the Pangan (0.2132) followed by the Bamon (0.0945) and the Kabui (0.0784) (Table 2).

Discussion

The Kabui tribe of the present study, with a relatively higher frequency of NESTROFT-positives, significantly differs from the Lotha tribe of Nagaland (Murry et al., 2003). This high frequency of NESTROFT-positives among Kabuis could be attributed to their migration from Southeast Asia where HBE and thalassaemia are found to be frequent (Nancy et al., 2008). A founder effect among them due to their short history in the region and the operation of natural selection cannot be ruled out as Manipur has a history of malarial endemicity.

NESTROFT is a general test for abnormal haemoglobins, and related reported data among the populations of the northeastern region is limited. As HBE and thalassaemia are abnormal haemoglobins, the present NESTROFT results can be compared with the available data on HBE and thalassaemia among various populations in and around the northeastern regions (Chakravartti and Roy, 1979). The relatively higher frequencies of NESTROFT-positives among the Bamons as compared to the Pangans agree well with the previous studies on HBE frequency among the Meitei and Bamon (Chakravartti and Roy, 1979; Singh et al., 1986).

The Pangans of the present study show NESTROFT-positive and NESTROFT-doubtful frequencies of 3.31% and 1.32%, respectively, which are certainly much lower than those among the Kabuis (13.51% and 24.32%, respectively) and the Bamons (10% and 11%, respectively). A cumulative high frequency of HBAE and HBEE (19.23%) has been reported among the Muslims of Assam (Deka et al., 1988) and a relatively low frequency (4.71%) was found among the Bengali Muslims of Bangladesh (Papiha et al., 1975). A lower frequency of NESTROFT-positives among the Pangans may be attributed to their migration from the area which is now in Bangladesh.

Regarding the G6PD deficiency, the Pangans significantly differ from Muslims of Assam (ICMR Project Report, 2003–2005) and Muslims of Bangladesh (Papiha et al., 1975) and do not differ significantly from Muslims of West Bengal. The high frequency of G6PD deficiency among the Pangans could also be because of the inflow of genes from West Bengal, where a high frequency of G6PD deficiency is reported, followed by natural selection due to malaria coupled with high consanguinity.

The frequencies of G6PD deficiency among the Bamon and Kabui are comparable and within the reported ranges of those of the neighbouring populations of northeastern India (Seth and Seth, 1971; Kar et al., 1992). As compared to Brahmins of Assam, the Bamons of the present study show a significant difference (χ² = 14.6, P = 0.001) (ICMR Project Report, 2003–2005) in the distribution of the G6PD deficiency, whereas they show non-significant (χ² = 1.57, P = 0.456) differences with the Brahmins of West Bengal.

In general, HBE frequency is high among northeastern states and thus high NESTROFT-positive frequencies found in the present study could be because of HBE. Although thalassaemia frequency is low in the northeastern states (Chakravartti and Roy, 1979), high frequencies of NESTROFT-positives among these populations could be fatal in combination with HBE.

The significant differences observed in the distribution of haemoglobinopathies and G6PD deficiency among the studied populations may be due to the maintenance of their own gene pools by strict endogamy. Earlier studies (Tripathy and Reddy, 2007; Viroj, 2008) have shown that haemoglobinopathies and G6PD deficiency have positive selection against the Plasmodium falciparum malaria. As the incidence of P. falciparum malaria is alarmingly high in Manipur, the prevalence of haemoglobinopathies and G6PD deficiency among these populations is not surprising. These two traits, therefore, might be showing balanced polymorphism vis-à-vis P. falciparum malarial prevalence.

The presence of G6PD deficiency in such a high frequency alongside the endemic P. falciparum malaria poses a serious public health problem for the people of Manipur and neighbouring states. The prescription of certain antimalarial drugs without checking for G6PD deficiency status may cause serious health consequences among these populations. Thus screening the populations for HBE and thalassaemia will help in preventing the population from the combined effect of thalassaemia and HBE.

Acknowledgment

We are very thankful to all our lab colleagues from the Biochemical Genetics Laboratory, Department of Anthropology, University of Delhi. We are also grateful to all the individuals who volunteered to participate in this study.