Genetic variability of transferrin subtypes in the populations of India

S.S. MASTANA1 AND S.S. PAPIHA

Abstract Five hundred fifteen samples from five populations of India (Brahmins, Marathas, Patels, and Parsees of western India and Hindus of Andhra Pradesh) were analyzed for transferrin subtypes using the isoelectric focusing technique. The allele frequencies of 8444 samples belonging to 93 populations of India have been tabulated, and data were analyzed for genetic diversity among geographic, regional, and sociocultural groups. Three relatively common alleles, TF*CI, TF*C2, and TF*C3, showed wide variation in various populations of India. Compared with western India, a high frequency of the TF*C2 allele was observed in eastern India. This variation of the TF*C2 allele showed a geographic cline increasing from west to east, giving a significant positive correlation between the TF*C2 allele frequency and longitude. Various genetic processes that possibly maintain TF polymorphism are selection, admixture, genetic drift, and isolation by distance. The possible influence of various genetic processes is discussed.

Polymorphism of the iron-binding protein transferrin (TF) was first described by Smithies (1957) using starch gel electrophoresis. Eighteen rare alleles at a single locus on chromosome 3q21 were described, mostly the fast-moving allele TF*B and the slow-moving TF*D allele, but the most common allele was TF*C, which was monomorphic in many populations. Subsequent analysis using isoelectric focusing demonstrated the existence of microheterogeneity of the TF*C allele, and to date, several codominant autosomal TF*C alleles (*CI, *C2, *C3, *C4, *C5, *C6, *C7, *C8, *CII, and *C12) have been identified in different world populations. Alleles TF*C1, TF*C2, and TF*C3 are relatively common, but other *C alleles have low frequencies and their distribution is limited to certain specific geographic areas (Walter 1996; Walter et al. 1983; Dykes et al. 1982).

Since the discovery of this microheterogeneity of the TF locus, patterns of variation in gene frequencies among 93 socially and culturally diverse populations of India from different geographic areas have been studied (Walter et al. 1981, 1983; Kamboh 1984; Mukherjee et al. 1986; Reddy et al. 1984). Extensive ranges of variation have been observed for the TF*C1, TF*C2, and TF*C3 alleles. Our aim here is to search for factors that may influence the maintenance of this high degree of TF polymorphism in the populations of India.

Methods and Materials

As part of our genetic investigations among Indian populations, we collected 515 blood samples from 2 geographic areas (western India and southern India) belonging to 3 endogamous caste groups and 2 nontribal groups. Brahmins (n = 114), Marathas (n = 135), Gujarati Patels (n = 77), and Parsees (n = 31) were collected from Bombay and surrounding areas. A Hindu sample (mixed castes, n = 158) was collected from Hyderabad, Andhra Pradesh. Brahmin, Maratha, and Patel castes form the main strata of the Maharashtran population. The Parsees are an endogamous migrant population that immigrated from Iran in the sixth century.

Blood samples from two different field surveys were transported by air to the Department of Human Genetics, University of Newcastle upon Tyne, where plasma was separated and TF subtypes were studied following the modified method of Kuhnl and Spielmann (1978). In all, 93 populations of India with 8444 individuals were phenotyped. The gene frequencies were calculated by gene counting. Hardy-Weinberg equilibrium was tested by a chi-square test. Pearson's correlation coefficient was determined using the available computer software. Correspondence and spatial autocorrelation analyses were performed using the methodology of Greenacre (1984) and Sokal and Oden (1978). Results

Gene frequencies of the TF subtypes among the five studied groups along with the frequencies of TF subtype alleles so far reported from different populations of India are listed in Table 1. The phenotype numbers of TF subtypes among the five population groups are not given (data available from authors), but the observed numbers in all populations were in good agreement with Hardy-Weinberg expectations.

The distribution of TF phenotypes in the population groups of western India showed significant genetic heterogeneity (,yz = 22.5, d.f. = 6; p

The previously described TF*C4 allele in Parsees was not observed in the present Parsee samples (Undevia and Saha 1987).

The range of genetic variation for alleles TF*CI, TF*C2, and TF*C3 is remarkable. The frequency of TF*C1 ranges from 38% in Sidhis (Karnataka tribe) to 80% in the Lepchas of West Bengal. Our present study in Marathas (Maharashtra caste) extends the upper range of the TF*CI allele to 87%.

The TF*C2 allele shows the opposite trend with the lowest value in the Marathas (9%) and the highest value in the Sidhis (61%). The TF*C3 allele frequency showed low values, and it is absent in several of the studied groups; however, its value is highest in the Vaish caste group from Delhi (10%).