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An expanded histatin gene polymorphism and test of a possible disease resistant phenotype
Author(s) -
Araki Motohide,
Anstey Nicholas M.,
Mwaikambo Esther D.,
Dua Arnavaz,
Amberger Ed,
Azen Edwin A.
Publication year - 1997
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/(sici)1098-1004(1997)10:1<58::aid-humu8>3.0.co;2-i
Subject(s) - biology , phenotype , gene , genetics , polymorphism (computer science) , disease , genotype , medicine
Histatins are small molecular weight salivary proteins that are important in the non‐immune host defense system. Two frequent cis‐linked coding‐change mutations were previously described in exon 5 of the HIS 2 gene of Blacks. The polymorphic mutant allele was termed HIS 2 2 and the wild‐type allele HIS 2 1 . We here describe two new non‐coding change polymorphisms of the HIS 2 gene: a deletion in intron 5 (7183‐7198 del) and a C⇒T mutation in exon 5 [C⇒T (7104)] that characterize two new HIS 2 alleles, HIS 2 3 and HIS 2 4 respectively. Both mutations occur on a HIS 2 1 background. The HIS 2 3 allele occurred only in Afro‐Americans, but not in 67 Japanese, 51 Chinese and 50 Whites. Among 66 random DNA samples from Afro‐Americans, frequencies of HIS 2 1 , HIS 2 2 , HIS 2 3 and HIS 2 4 were 0.67, 0.22, 0.05 and 0.07 respectively, with a heterozygosity of 0.45. The frequencies of the HIS 2 4 allele in 50 Whites and 50 Chinese were 0.06, and 0.1 respectively. In a comparison of 60 matched saliva and DNA samples from the Afro‐American population, the DNA‐based mutation analysis reliably identified salivary histatin phenotypes. The salivary histatin polymorphism (inferred from PCR analysis) was used to test a biologically plausible hypothesis, that the mutant histatin phenotype (coded by the HIS 2 2 allele) confers relative resistance to severe and fatal malaria. In a study of 185 Black Tanzanian subjects, there were no significant differences in HIS 2 2 allelic frequencies between the various test groups: for 86 cerebral malaria subjects, 54 uncomplicated malaria subjects, and 45 combined asymptomatic parasitemia and health controls, HIS 2 2 frequencies were 0.16, 0.17 and 0.17 respectively. Thus, there was no support for the hypothesis in this population. Hum. Mutat. 10:58–64, 1997. © 1997 Wiley‐Liss, Inc.