Association Between G-6-PD Gene Polymorphism And G-6-PD Deficiency

Objective:(1)To investigate the mutation distribution of glucose-6-phosphate dehydrogenase(G6PD)gene.(2)To explore the correlation between G6 PD gene polymorphism and G6 PD deficiency.(3)To investigate the correlation between G6 PD gene polymorphisms and clinical phenotypes.Methods:(1)From February 2019 to December 2019,the patients with G6 PD deficiency and the control with normal G6 PD enzyme content were randomly selected from the Zhuang and Han population in the genetic outpatient clinic of Youjiang Medical College of nationalities as research objects.G6 PD enzyme activity was determined by Hitachi 7600-series automatic biochemical analyzer.Automatic blood cell analyzer was used to detect blood routine and other related indexes.(2)SNPscan TM multiple SNP typing technique was used to detect the 35 G6 PD mutation types,then each genotype in the gene locus was analyzed.The genotypes in gene loci were statistically analyzed.The relationship between G6 PD gene polymorphisms and clinical phenotypes were analyzed.The differences in G6 PD genotype frequency and allele frequency distribution of different genders and different ages were compared.(3)The online haplotype analysis software(SHEsis software)was used to analyze the haplotype distribution frequency of the G6 PD deficiency case group and the G6 PD enzyme content normal group.Results:(1)A total of 417 patients with G6 PD deficiency and 295 patients with normal G6 PD enzyme content were selected as control group.The prevalence rate of men was higher than that of women(P<0.001),and there was no statistical difference between Zhuang and Han groups(P=0.338).(2)A total of 13 single-point mutations,6 complex mutation types and 7 triple mutation types of G6 PD genes were detected in the G6 PD deficiency case group.The main gene mutation types were: c.1388G>A,c.1376G>T,c.95A>G and c.1024C>T.which accounted for73.14% of the total.(3)The distribution frequency of alleles at different G6 PD locus is different between the G6 PD deficiency case group and the G6 PD enzyme content normal group.There is a significant difference in the distribution of the allele A of 1388G>A,the allele T of c.1376G>T,the allele G of c.95A>G and the allele T of c.1024C>T between the G6 PD deficiency group and the G6 PD enzyme content normal group(P<0.001,OR=5.598;P<0.001,OR=10.288;P<0.001,OR=4.608;P<0.001,OR=9.232).(4)Comparing the genotypes at different sites of G6 PD with the risk of G6 PD deficiency showed that c.1388G>A co-dominant model GA,AA,recessive model AA and dominant model GA+AA all increased the risk of G6 PD deficiency;c.1376G>T loci GT genotypes,dominant model GT TT all increased the risk of G6 PD deficiency;c.95A>G co-dominant model AG、GG、 recessive model GG、 dominant model increased the risk of G6 PD deficiency;c.1024C>T co-dominant model CT、 dominant model CT TT increased the risk of G6 PD deficiency.There was no significant difference between c.1376G>T co-dominant model TT,recessive model TT and c.1024C>T co-dominant model TT,recessive model TT between the G6 PD lacking case group and the control group.(5)The haplotype analysis showed that there were five haplotypes,mainly A-G-C-A、G-G-C-G、G-G-T-A、G-T-C-A and G-G-C-A,which were statistical difference between the G6 PD deficiency group and the normal G6 PD enzyme content group(P<0.001).The distribution frequency of the four haplotypes in the G6 PD deficiency group was higher than that in the normal group,which increased the risk of patients with G6 PD deficiency.The distribution frequency of G-G-C-A haplotypes in the G6 PD deficiency group was lower than that in the normal G6 PD enzyme group,which may play a protective role in the occurrence of G6 PD deficiency.(6)Among the four main mutation sites,the G6 PD enzyme activity expression level at the c.1376G>T mutation site was the lowest,which was different from those at the c.1388G>A and c.1024G>T mutation sites.(c.1388G>A vs c.1376G>T : P=0.037;c.1024C>T vs c.1376G>T:P=0.022).Conclusion:(1)In this study,26 types of G6 PD gene mutations were detected in patients with G6 PD deficiency.The main types of mutations were: c.1388G>A,c.1376G>T,c.95A>G and c.1024C>T.(2)Mutant gene types that cause G6 PD deficiency are complex,with single-point mutations,complex mutations,and even triple mutations.The study found 13 single-point mutations,six complex mutations,and seven triple mutations.(3)The four haplotypes A-G-C-A、G-G-C-G、G-G-T-A、G-T-C-A all four haplotypes all increased the risk of G6 PD deficiency,while G-G-C-A haplotypes played a protective role in the risk of G6 PD deficiency.(4)C.1388G>A、c.1376G>T、c.95A>G and c.1024C>T of G6 PD main mutation sites decreased the expression level of G6 PD enzyme activity.Among them,patients with c.1376G>T mutation site had the lowest expression level of G6 PD enzyme activity.