The mutation spectrum of the JK‐null phenotype in the Chinese population

Abstract

BACKGROUND: This study aimed to analyze the mutation spectrum of the JK‐null phenotype in the Chinese population. The JK gene encoding the Kidd blood group antigen protein and JK*A/JK*B polymorphism caused by a G‐to‐A mutation at nt838 are well described. However, the molecular basis of the JK‐null phenotype in Chinese populations remains unclear. STUDY DESIGN AND METHODS: Sixteen unrelated JK‐null phenotype donors detected by red blood cell urea lysis resistance assay of 201,194 Chinese blood donors were confirmed in serologic agglutination tests. JK‐null alleles were analyzed by MnlI polymerase chain reaction–restriction fragment length polymorphism and sequencing of all JK gene coding regions. RESULTS: In addition to the well‐known Polynesian JK‐null allele JK*B(IVS5‐1g>a) and two alleles discovered in Taiwan, JK*B(896G>A) and JK*B(222C>A), seven JK‐null allele types were detected in this study including four novel JK‐null alleles: a nonsense mutation, JK*B(512G>A); two types of missense point mutations, JK*B(536C>G) and JK*B(437T>C); and a splice mutation, JK*A(IVS8+5g>a), resulting in skipping of Exon 8. CONCLUSION: This study demonstrates the frequency and heterogeneity of the JK‐null phenotype in Chinese populations. Based on our findings, the mechanisms underlying the Chinese Jk(a−b−) phenotype are quite different from other ethnic groups. The two most common types of JK‐null alleles were JK*B(IVS5‐1g>a) and JK*B(896G>A) in Chinese persons. Four novel JK‐null alleles were noted to be associated with the Jk(a−b−) phenotype.

Red blood cell genotyping in China

“…This rare phenotype has been reported with the highest frequency in Polynesians (0·1–1·4%). In the Chinese populations, the frequency of JK(a‐b‐) in the southern regions is about 1:5000 (10/50 000 in Guangzhou), which is higher than some other reported regions (1:20 000 in Changchun ; 1:25 000 (4/102 760 and 2/48 400) in Shanghai ; 1:17000–1:20 000 (3/52 260 to 2/40 337 ) in Nanjing; not found (0/23 909) in Zhejiang ) using the red blood cell urea lysis resistance assay for screening. Several patients with anti‐Jk3 were also encountered in Guangzhou .…”

“…At least 50 probands with JK(a‐b‐) phenotype were identified in the Chinese population for JK genotyping analysis (Table ) . Among them, nine mutations of JK gene were found, in which seven mutations occured on the JK*B allele and two on the JK*A allele.…”

“…Further, the urea lysis resistance method is a very cheap and feasible method that could be used for screening the JK (a-b-) blood on a large scale. At least 50 probands with JK(a-b-) phenotype were identified in the Chinese population for JK genotyping analysis ( Table 6) [99][100][101][102][106][107][108][109]. Among them, nine Table 5 The distribution of the reported FUT2 genotypes in the Chinese individuals with para-Bombay phenotype…”

Production of human monoclonal anti‐Jk3, recognising an epitope including the Jka/Jkb polymorphic site of the Kidd glycoprotein

“…Recently, more than 24 silencing mutations were identified from Jk(a−b−) individuals (Lucien et al , ; Billingsley et al , ; Horn et al , ; Sriwanitchrak et al , ; Guo et al ., ; St‐Louis et al , ; Onodera et al , ), and it appeared to be difficult to type them by using a simple and cheap genotyping method. In contrast, monoclonal anti‐Jk3 produced in this study (HIRO‐294) will be useful method with a cost benefit for confirming the Jk(a−b−) phenotype.…”

“…Recent molecular genetic studies revealed diversity of JK null alleles having many different mutations (Lucien et al , ; Billingsley et al , ; Horn et al , ; Sriwanitchrak et al , ; Guo et al ., ; St‐Louis et al , ; Onodera et al , ) that appeared to be difficult to identify by conventional genotyping. In accordance with the above observations, anti‐Jk3 is still useful for Jk(a−b−) typing.…”