The population of India is extremely diverse comprising of more than 3,000 ethnic groups who still follow endogamy. Haemoglobinopathies are the commonest hereditary disorders in India and pose a major health problem. The data on the prevalence of β-thalassemias and other haemoglobinopathies in different caste/ethnic groups of India is scarce. Therefore the present multicentre study was undertaken in six cities of six states of India (Maharashtra, Gujarat, West Bengal, Assam, Karnataka and Punjab) to determine the prevalence of haemoglobinopathies in different caste/ethnic groups using uniform methodology. Fifty-six thousand seven hundred eighty individuals (college students and pregnant women) from different caste/ethnic groups were screened. RBC indices were measured on an automated haematology counter while the percentage of HbA2, HbF and other abnormal Hb variants were estimated by HPLC on the Variant Hemoglobin Testing System. The overall prevalence of β-thalassemia trait was 2.78 % and varied from 1.48 to 3.64 % in different states, while the prevalence of β-thalassemia trait in 59 ethnic groups varied from 0 to 9.3 %. HbE trait was mainly seen in Dibrugarh in Assam (23.9 %) and Kolkata in West Bengal (3.92 %). In six ethnic groups from Assam, the prevalence of HbE trait varied from 41.1 to 66.7 %. Few subjects with δβ-thalassemia, HPFH, HbS trait, HbD trait, HbE homozygous and HbE β-thalassemia as well as HbS homozygous and HbS-β-thalassemia (<1 %) were also identified. This is the first large multicentre study covering cities from different regions of the country for screening for β-thalassemia carriers and other haemoglobinopathies where uniform protocols and methodology was followed and quality control ensured by the co-ordinating centre. This study also shows that establishment of centres for screening for β-thalassemia and other haemoglobinopathies is possible in medical colleges. Creating awareness, screening and counselling can be done at these centres. This experience will help to formulate a national thalassemia control programme in India.

Prevalence of β-thalassemia and other haemoglobinopathies in six cities in India: a multicentre study

The β-thalassemias, including the hemoglobin E disorders, are not only common in the Mediterranean region, South-East Asia, the Indian subcontinent and the Middle East but have now become a global problem, spreading to much of Europe, the Americas and Australia owing to migration of people from these regions. Approximately 1.5% of the global population are heterozygotes or carriers of the β-thalassemias. While the overall frequencies of carriers of these disorders are known in most countries, there have been few attempts at micromapping and wherever this has been done, significant variations are seen even within small geographic regions. Thus, the figures for the estimated numbers of births each year of homozygous β-thalassemia and the severe compound states involving other hemoglobin disorders may be an underestimate. Screening strategies have varied from premarital to antenatal in different countries depending on socio-cultural and religious customs in different populations. Prenatal diagnosis programs are ongoing in many countries and the knowledge of the distribution of mutations has facilitated the establishment of successful control programs. Many of these were through North-South partnerships and networking. Yet, there are many countries in Asia where they are lacking, and South-South partnerships are now being developed in South-East Asia and the Indian subcontinent to link centers with expertise to centers where expertise needs to be developed. Although the carrier frequencies will remain unaltered, this will eventually help to bring down the burden of the birth of affected children with β-thalassemias and hemoglobin E disorders in Asia.

Global burden, distribution and prevention of β-thalassemias and hemoglobin E disorders

The frequencies of hemoglobin E and βE-globin gene haplotypes were determined in eight minority groups living in the northeastern part of Thailand. A total of 478 samples of eight minority

Frequency Distribution and Haplotypic Heterogeneity of βE-Globin Gene among Eight Minority Groups of Northeast Thailand

The thalassaemias and sickle cell disease are the commonest monogenic disorders in India. There are an estimated 7500 - 12,000 babies with β-thalassaemia major born every year in the country. While the overall prevalence of carriers in different States varies from 1.5 to 4 per cent, recent work has shown considerable variations in frequencies even within States. Thus, micromapping would help to determine the true burden of the disease. Although screening in antenatal clinics is being done at many centres, only 15-20 per cent of pregnant women register in antenatal clinics in public hospitals in the first trimester of pregnancy. There are only a handful of centres in major cities in this vast country where prenatal diagnosis is done. There is considerable molecular heterogeneity with 64 mutations identified, of which 6 to 7 common mutations account for 80-90 per cent of mutant alleles. First trimester foetal diagnosis is done by chorionic villus sampling (CVS) and DNA analysis using reverse dot blot hybridization, amplification refractory mutation system (ARMS) and DNA sequencing. Second trimester diagnosis is done by cordocentesis and foetal blood analysis on HPLC at a few centres. Our experience on prenatal diagnosis of haemoglobinopathies in 2221 pregnancies has shown that >90 per cent of couples were referred for prenatal diagnosis of β-thalassaemia after having one or more affected children while about 35 per cent of couples were referred for prenatal diagnosis of sickle cell disorders prospectively. There is a clear need for more data from India on non-invasive approaches for prenatal diagnosis.

Invasive & non-invasive approaches for prenatal diagnosis of haemoglobinopathies: experiences from India.

Several gene mutations are associated with an increased risk of Alzheimer's disease. Previous studies reported higher transferrin C2 allele frequencies in Alzheimer's disease compared with normal controls. However, potential interactions between transferrin C2 and APOE (epsilon 4), have not been extensively investigated and have been the subject of controversial reports from several laboratories. We have carried out a case-control study on the association between Alzheimer's disease and transferrin C2 and APOE epsilon 4 alleles. epsilon 4 allele was associated with a four fold increase in the risk of disease, and transferrin C2 allele was significantly associated with Alzheimer's disease only in epsilon 4 negative subjects. These results suggest that apoE and transferrin may be part of a complex mechanism in the pathogenesis of Alzheimer's disease.

Transferrin C2 variant does confer a risk for Alzheimer's disease in caucasians.

Previous studies have reported a high incidence of hemoglobin E (HbE) in Northeast Indian populations. In the present study 10 endogamous populations of Assam belonging to two racial groups, Caucasoid and Mongoloid, were examined. The frequency of HbE gene (Hb βE) in the Caucasoid caste populations is around 0.1, whereas the gene is highly prevalent in the Mongoloid populations, frequencies ranging between 0.2 and 0.6. Predominance of Hb βE in the Tibeto-Burman speakers is contrary to observations made in Southeast Asia, where an association between Austro-Asiatic speakers and high prevalence of HbE exist. The highest occurrence of the gene in this area, which is on the far end of the proposed centre of distribution in Northern Kampuchea and Northeast Thailand, is also a deviation from the expected pattern of gene distribution. It is speculated that Hb βE in the Tibeto-Burman populations of Assam arose by an independent mutation which contributed to the high frequencies of Hb βE in the Northeast Indian populations.

Hemoglobin E Distribution in Ten Endogamous Population Groups of Assam, India

18 polymorphic systems of the blood ? A1A2BO, MNSs, Rhesus (C,c,D,E,e), Duffy, Diego; Haptoglobin (Hp), Ceruloplasmin (Cp), Transferrin subtypes (Tf), Gc subtypes (Gc), Gm (1,2,5), Km (1); red cell acid phosphatase (aP), phosphoglucomutase subtypes (PGMi), adenylate ki nase (AK), adenosine deaminase (ADA), esterase D (EsD), lactate dehydrogenase (LDH), and hae moglobin variants were typed on 237 Siddis from Karnataka (South India), a Negroid population of African descent, which came to India at various periods, starting as early as 1100 AD They were mainly imported as slaves The typing results were compared with that of two other population groups of Karnataka: Havig Brahmins (n = 140) and Muslims (n = 27) as well as with pooled samples of Ethiopia It is seen that the genetic pattern of the Siddis is much more similar to that of Ethiopians than to Havig Brahmins or Muslims One can assume that this is due to the genetic isolation of the Siddis, though some gene flow from Indian side cannot be ruled out completely

Genetic studies among the Siddis of Karnataka, India: A migrant population from Africa

Transferrin subtyping by isoelectrofocusing in three West Bengal populations.

Transferrin subtypes have been determined by isoelectric focussing of sera from 536 individuals belonging to 9 South Indian populations: Vaidic Brahmins and Vaysya from Andhra Pradesh; Havik Brahmin,

Patterns of social and geographical distribution of transferrin subtype polymorphism in India.

Red cell hemolysates from 1,004 persons belonging to 14 population groups drawn from four South Indian states, Andhra Pradesh, Tamil Nadu, Karnataka, and Kerala, were tested for PGM1 subtypes. The groups are characterized by a high frequency of phenotype 1+1+ (range 36.98-71.64%) and the allele 1+ (range 60-79%). The groups exhibit marked heterogeneity for PGM1 locus. The results show a clear demarcation between tribes and Brahmin groups.

A. P. Reddy

Papers

Hemoglobin E Distribution in Ten Endogamous Population Groups of Assam, India

Genetic studies among the Siddis of Karnataka, India: A migrant population from Africa

Transferrin subtyping by isoelectrofocusing in three West Bengal populations.

Patterns of social and geographical distribution of transferrin subtype polymorphism in India.

PGM1 subtype polymorphism in 14 endogamous Dravidian-speaking populations of South India.