Download Glucose-6-Phosphate Dehydrogenase (GGPD) Mutations

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3767
CORRESPONDENCE
Glucose-6-Phosphate Dehydrogenase(GGPD) Mutations Associated With F8C/G6PD Haplotypes in Chinese
To the Editor:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency isthe
most common human disease producing red blood cell enzyme deficiency.’ Nearly 400 biochemical variants have been described, but
less than 70 mutations have been identified attheDNA
level.
We2-5and others”’ have previously shown that at least nine different
types of mutation are responsible for G6PD deficiency in the Chinese
population of Taiwan. The finding that several polymorphic sites
are located near or within the G6PD gene may provide a haplotype
pattern that would enable us to analyze the linkage disequilibrium
between mutations and polymorphisms.
The F8C/G6PD (coagulation factor VIIIc/G6PD) haplotype”
spanning the Xq28 region from coagulation factor VIIIc to the G6PD
genes was investigated. We have studied four polymorphic sites
from this region in 66 Chinese who carry known G6PD mutations.
These polymorphic sites include (1) the Hind111 site in intron 19 of
the factor VI11 gene,” (2) the 1311 C-tT mutation ofthe G6PD
gene,” (3) the polymorphic Nlu I11 site in intron 11 of the G6PD
gene,” and (4) the polymorphic EcoRI site located 20 kb downstream
of the G6PD gene.l4 Table 1 shows that most mutations found in
Chinese are mainly associated with haplotype VI + VII, ie, -- - +
(FSHindIII/131l/Nlu IWEcoRI), except for three types of mutation
that occur at nucleotide (nt) positions 392, 871, and 1376 that appear
to be associated with different haplotypes. For example, 29 of 31
Chinese subjects with the 1376 mutation are mainly associated with
haplotype 111, whereas all of the 871 mutation cases are linked to a
novel haplotype that we name here haplotype XI that has not been
reported before. Interestingly, our unpublished data show that haplotype VI + VI1 is the dominant haplotype that accounts for nearly
80% of the normal Chinese population in Taiwan (manuscript in
preparation). These findings support the hypothesis that mutations
occurring at nt positions 95, 487, 493, 1024, 1360, and 1388 could
a l r k derived from an ancient haplotype VI + VII.
The 1376 mutation was found to be not only associated with haplo-
type III (29 cases) but also linked to two other haplotypes (1 case in
haplotype I and 1 case in haplotype VI + VII). This result suggested
that the mutation at nt 1376 may have arisen repeatedly or a crossingover event may have occurred between F8C and the
M P D gene or
within the G6PD gene itself. In addition, by comparative analysis of
the association between the 871 mutation and the 1311 polymorphic
site, we found that Chinese subjects who carry the 871 mutation have
Viang~han”’~
(a
T at nt1311, as waspreviouslyfoundinG6PD
Laotian).l5In contrast, G6PD J a m m ~ ” ’(a~ variant originally detected
in an Indiansubject)”has a C at nt 131 1, suggestingthatthe871
Table 1. Linkage Analysis Between Mutations and FBCIGGPD
Haplotypes in Chinese Subjects From Taiwan
GGPD
Mutations
95A-G
392G+T
487 G + A
493A-G
871 G - A
1024C-T
1360C-T
1376 G + T
1388 G + A
N
FBHindlll
1311T
Nla Ill
EcoRl
6
3
1
8
3
7
2
29
1
1
4
1
-
-
-
+
-
-
+
+
+
+
+
-
-
-
-
-
-
Haplotypes’
VI
Ill
VI
VI
XI
VI
VI
111
+ VI1
+ VI1
-
+
+
-
-
-
-
-
-
+
-
-
-
-
-
+
VI
-
-
-
+
+
VI
111
+
+
+
+
+
+
+
+
+ VI1
+ VI1
+ VI1
+ VI1
I
-
+ VI1
”+“ indicates if restriction site is present or if 1311 C T mutation
is present. n indicates the number of affected male subjects analyzed.
* The F8C/G6PD haplotypes were named as described by Filosa et
al.’” Because we did not analyze the polymorphic Xba I site in F8C
gene, haplotyes VI and VI1 cannot be distinguished in our studies.
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CORRESPONDENCE
3768
mutations may have arisen separately.Our findmgs are consistent with
whoanalyzedtheG6PDhaplotypethat
that reported byXu et
carried different polymorphic sites located
at intron 5 (Pvu II), nt 11 16
(Pst I), nt 1311, and intron 11 (Ma III) of the G6PD gene. Finally,we
found that most 1388 mutations were associated with haplotype VI +
VII, whereas only 1 case was found to be associated with haplotype
III. This particular case could$ave been generated by a recombination
event that took place somewhere between F8C and G6PD genes at a
later stage.
In summary, we have analyzed the association between G6PD
mutations and F8CIG6PD haplotypes and found a strong linkage
disequilibrium between some of the G6PD mutations and F8C/
G6PD haplotypes. This information may provide some useful information for tracing the diversity of various ethnic populations
in the world.
ACKNOWLEDGMENT
This work is supported by an Institutional grant from Academia
Sinica and by a grant from the National Science Council, Republic
of China. The authors thank Ching-Shan Huang and May-Jen Huang
for making available samples for study. Part of this work was included in the thesis of Te-Hui Liu for Master of Science, Department
of Zoology, National Taiwan University.
Tang K. Tang
Te-Hui Liu
Chieh-Ju Chang Tang
Ka-Bik Tam
Institute of Biomedical Sciences
Academia Sinica
Taipei, Taiwan
China
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From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1995 85: 3767-3768
Glucose-6-phosphate dehydrogenase (G6PD) mutations associated
with F8C/G6PD haplotypes in Chinese [letter]
TK Tang, TH Liu, CJ Tang and KB Tam
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