A−61C and C−101G Hp gene promoter polymorphisms are, respectively, associated with ahaptoglobinaemia and hypohaptoglobinaemia in Ghana

Abstract

We have investigated the genetic basis for the Hp0 phenotype amongst 123 randomly selected Ghanaians. A total of 17 individuals were determined to be Hp0 phenotype, based on the classical method for Hp phenotyping of Hb-supplemented plasma. Out of the 17 Hp0 individuals, nine subjects were further classified as ahaptoglobinaemic and eight as hypohaptoglobinaemic by Western blots and double immunodiffusion. We identified three previously known base substitutions (A-55G, A-61C and T-104A) and three new ones (C-101G, T-191G and C-242T) within the 5' flanking region of the Hp gene. The A-61C base substitution significantly decreased transcriptional activity and was associated strongly with Hp2 allele and ahaptoglobinaemia. The C-101G substitution was similar in transcriptional activity to the wild-type and was associated with Hp1S allele and hypohaptoglobinaemia. The Hpdel allele seen in Asian populations was absent. We conclude that the Hp0 phenotype in Ghana has a genetic basis that differs significantly from that seen in Asia.

Rapid Detection of Haptoglobin Gene Deletion in Alkaline-Denatured Blood by Loop-Mediated Isothermal Amplification Reaction

“…In addition, only HP-5= tubes were positive when using DNA of three Ghanaians with acquired anhaptoglobinemia (without any causal mutations in the promoter and coding regions) as templates. 6 The threshold time required for the turbidity of the solution to develop was about 25 minutes for HP-del and about 23 minutes for HP-5=. After amplification, all of the positive reactions produced white precipitates and a characteristic ladder of multiple bands on an agarose gel, whereas no bands were detected in negative controls.…”

“…4,5 The HP del allele has been found only in East and Southeast Asian populations (Chinese, Korean, Japanese, Mongols, Thais, and Indonesians), not in African, West and South Asian, and European populations so far. [5][6][7][8][9] Detection of homozygosity for HP del before blood transfusion or blood component infusion is important to prevent severe side effects of transfusion because washed red blood cells and platelet concentrate do not cause transfusion-related anaphylactic reactions. 10 Recently, we established two real-time PCR methods for detection of HP del by use of a 5=-nuclease assay using dual-labeled (TaqMan; Applied Biosystems, Foster City, CA) probes and SYBR Green I (Invitrogen, Carlsbad, CA).…”

Smokers are Over-Represented in Subjects with Ahaptoglobinemia in Ghana

“…Ahaptoglobinemia has been established to be due to environmental and genetic factors in all populations 15,16,21,22) . The environmental factors precipitate hemolysis either intravascularly or extravascularly, leading to depletion of haptoglobin as it mops up released hemoglobin.…”

“…Haptoglobin exists as three polymorphs in humans, namely Hp1-1, Hp2-1, and Hp2-2 14) . A fourth phenotype, Hp0 (ahaptoglobinemia or hypohaptoglobinemia), has been shown to have both genetic and environmental causes 15,16) . In Africans, the genetic cause of ahaptoglobinemia and hypohaptoglobinemia has been established to be due to two mutations (A-61C and C-101G) in the promoter region of the Hp gene 15) .…”

“…A fourth phenotype, Hp0 (ahaptoglobinemia or hypohaptoglobinemia), has been shown to have both genetic and environmental causes 15,16) . In Africans, the genetic cause of ahaptoglobinemia and hypohaptoglobinemia has been established to be due to two mutations (A-61C and C-101G) in the promoter region of the Hp gene 15) . The major environmental factor responsible for ahaptoglobinemia in sub-Saharan Africa is infection with P. falciparum 16) .…”