Haptoglobin genotyping of Vietnamese: Global distribution of HPdel, complete deletion allele of the HP gene
Introduction
Haptoglobin (HP) is a plasma glycoprotein and is known to be one of the acute phase reactants [1], [2]. It binds hemoglobin (Hb) to prevent both iron loss and kidney damage due to oxidative activity of Hb during intravascular hemolysis [3]. Humans have a genetic polymorphism of the protein due to two codominant alleles, HP1 and HP2, that give rise to the three common phenotypes HP1-1, HP2-1, and HP2-2 [3]. According to this polymorphic feature, HP had been used as a genetic marker in determinations of parentage. The HP gene locates on the long arm of chromosome 16 (16q22.3) and consists of five (HP1) or seven (HP2) exons. HP2 appears to have been generated by a 1.7-kb intragenic duplication of exons 3 and 4 of HP1. Both HP1 and HP2 have been found in every population examined, although their frequencies vary considerably among populations [3], [4].
In addition to common polymorphisms, several rare variants of the HP phenotypes have been reported [3]. One of them is the HP-gene deletion allele (HPdel), which has an approximately 28 kb deletion extending from the HP promoter region to intron 4 of the HP-related gene. We identified HPdel by genetic analysis of several Japanese cases with a negative result only for HP inheritance encountered in determinations of parentage performed in forensic practice [5]. This silent allele allows us to interpret many cases with “incompatible” heredity. HPdel homozygotes produce no HP protein and are phenotypically anhaptoglobinemic, while HPdel heterozygotes have a lower amount of HP protein in their serum than those without HPdel [5], [6]. HPdel homozygotes have a risk of undergoing anaphylactic transfusion reactions if they produce HP antibodies [7]. Because washed red blood cells and platelet concentrate are effective in preventing transfusion-related anaphylactic reactions [8], we have developed several simple methods to detect this allele before transfusion [7], [9], [10], [11]. A series of studies by several groups including us have found HPdel in East and Southeast Asian populations but not in others [6], [7], [9], [12], [13], [14], [15], [16], [17]. For better understanding of the distribution of this allele in order to prevent serious problems in clinical practice and to determine whether it can be used as one of the ancestry informative markers, we determined the HP genotypes of a Vietnamese population in this study.
Section snippets
Samples
Blood samples of 293 local residents were randomly collected in Hoa Hau and Liem Thuan in March 2006 [18], Thanh Vanh and Thach Hoa in September 2007[18], and Thach Hoa, Son Dong, and Van Phuc in September 2008. All are communes located in the Red River Delta, Vietnam. Informed consent was obtained from all participants, and this study was approved by the Ethical Committee of Ehime University and Kurume University, Japan.
HP genotyping
Genomic DNA was extracted from the blood of 293 subjects using a QIAamp
Results and discussion
The real-time PCR method for determination of common HP alleles was based on comparative threshold cycles (CT) of the HP2-specific sequence (duplication junction) and a control sequence (5′ flanking sequence of exon 1 of HP) [20]. The previous population genetic analyses revealed that HPdel is distributed among East and Southeast Asians. The countries of Southeast Asia are geographically isolated from one another but are occupied by ethnically similar peoples [3]. The genetic variation of the
Acknowledgements
This work was supported by grants-in-aid for Scientific Research from the Ministry of Education, Science, Culture and Sports of Japan and grant from the Ishibashi Foundation for the Promotion of Science. The authors wish to thank the staff of the CETASD, Hanoi University of Science and Dr. Nguyen Minh Tue from CMES for their help in sample collection. The authors thank Ms. Katherine Ono for the English editing of this manuscript.
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Serum haptoglobin correlates positively with cholesterol and triglyceride concentrations in an obese Mongolian population
2020, Clinica Chimica ActaCitation Excerpt :The HP3 allele, which has a three-fold tandem repeat of the same 1.7-kb segment duplicated in HP2, accounts for the Johnson phenotype observed worldwide (Fig. 1) [12,13]. The HPdel allele, which lacks the promoter region of the HP to intron 4 of the HPR, is encountered only in East and Southeast Asian populations (Fig. 1) [14–17]. Recent studies have revealed that at least three genetic polymorphisms in the HP or HPR affect not only serum HP but also lipid concentrations as follows.
Association of the genetic variant rs2000999 with haptoglobin and diabetic macrovascular diseases in Chinese patients with type 2 diabetes
2019, Journal of Diabetes and its ComplicationsCitation Excerpt :There is a 1.7 kb intragenic duplication in the generalized defined Hp gene, including the CNV of the Hp 1 and Hp 2 alleles, producing three common Hp genotypes, Hp1-1, Hp2-1 and Hp2-2.19 Furthermore, a less common allele, Hpdel, lacking a 28-kb fragment that extends from the promoter region of the Hp gene to exon 5 of the HPR gene was identified.20 Therefore, the genetic variant rs2000999 was interrupted when Hpdel appeared.
The haptoglobin promoter polymorphism rs5471 is the most definitive genetic determinant of serum haptoglobin level in a Ghanaian population
2018, Clinica Chimica ActaCitation Excerpt :In addition, a haptoglobin gene deletion allele (HPdel) that we characterized as a causal mutation of anhaptoglobinemia also affects the concentration in heterozygotes especially in HP2/HPdel [5,6]. HPdel, which lacks an approximately 28-kb segment that extends from the promoter region to exon 5 of the haptoglobin-related gene (HPR), is found only in East and Southeast Asian populations with a frequency of 0.009–0.040 [7–12]. And rs2000999, which resides in intron 2 of the neighboring HPR, was identified as a strong genetic determinant of the serum HP level in Europeans [4,13] and Asians [6,12].
Haptoglobin polymorphisms in Latin American populations
2020, Scientific Reports