Identification of Two LDL-Receptor Mutations Causing Familial Hypercholesterolemia in Indian Subjects by a Simplified Rapid PCR-Heteroduplex Method

The molecular analysis of familial hypercholesterolemia (FH), an autosomal dominant disease caused by a multitude of LDL receptor (LDLR) gene mutations, is complicated by mutational heterogeneity of the disease in the majority of population studied to date (1). Exceptions occur where the frequencies of specific mutations are increased in a population because of founder effects, or where a mutation has been introduced on many occasions into a small isolated community (2)(3)(4). The prevalence of FH in India is not known. In addition, to the best of our knowledge there are no published reports on systematic analyses of mutations underlying FH in India. However, to date 10 different LDLR mutations in immigrants from India have been reported in the literature (5). Most of these mutations have been reported in exons 3, 4, 9, and 14 among Indians settled in South Africa, which suggests an increased frequency of FH in India (5). More than 80% of the 150 000 Indians who immigrated to South Africa between 1860 and 1911 originated from diverse areas in India (6). This group has remained isolated as a whole and also within different communities, primarily as a result of religious and cultural practices. This probably indicates that the increased incidence of mutations is attributable to multiple entries of defective LDLR genes into the Indian population of South Africa from India and that the group in South Africa probably represents the incidence in the Indian subcontinent.The current study …