The association between four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) and fetal hemoglobin levels in Chinese Zhuang β-thalassemia intermedia patients.
Four SNPs (rs7482144, rs4671393, rs28384513 and rs4895441) associated with HbF levels have been identified in different populations worldwide. To explore whether these SNPs modulate HbF expression in Chinese Zhuang population, 436 Chinese Zhuang β-thalassemia intermedia (β-TI) patients were divided into high HbF level group (mean HbF=25.5%, n=218) and low group (mean HbF=6.51%, n=218) for genotyping using PCR-HRM method. Results demonstrated that there was a significantly higher minor allele frequency (MAF=34.2%) of rs4895441 (G) in HMIP in high HbF level group than that in low group (MAF=19.8%) (P=0.001, OR=1.73, 95% CI: 1.24-2.57). The cumulative effects of risk genotypes of these loci for patients carrying any combination of 1, 2 or 3 risk genotype had a gradually increased risk of high HbF level phenotype compared to those without the risk genotypes (OR=1.50-9.06, P=0.0008); Gene-gene interaction of rs7842144 and rs4895441 showed the best model with the smallest prediction error (0.4259) and the greatest consistency of coefficient of variation (P=0.01). We concluded that rs4895441, G on HMIP might be a high-risk modifier variant for high HbF level expression, and HBG2, BCL11A and HMIP genes, as HbF quantitative trait loci (QTL) could have a synergistic effect on increasing the HbF level in Chinese Zhuang β-TI patients.
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Yunli
Y
Lai
Maternal and Child Health Hospital of Dongchangfu District of Shandong City, Liao Cheng 252200, PR China.
Lin
L
Zhou
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Sheng
S
Yi
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Yun
Y
Chen
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Yanqing
Y
Tang
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Shang
S
Yi
National Institute of Geriatrics, Beijing Hospital, Ministry of Health, Beijing 100730, PR China.
Ze
Z
Yang
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Hongwei
H
Wei
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.
Chenguang
C
Zheng
Guangxi birth defects prevention and Control Research Institute, Guangxi Zhuang Autonomous Region Women and Children Health Care Hospital, Nanning, Guangxi, PR China.. Electronic address: heshengbio@163.com.
Sheng
S
He
D000293:Adolescent; D000328:Adult; D044466:Asian People; D002352:Carrier Proteins / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D005260:Female; D005319:Fetal Hemoglobin / Q000032:analysis* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics; D005787:Gene Frequency; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics; D006801:Humans; D008297:Male; D009687:Nuclear Proteins / Q000235:genetics; D020626:Oncogene Proteins v-myb / Q000235:genetics; D010445:Peptide Elongation Factors / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins; D055815:Young Adult; D017086:beta-Thalassemia / Q000097:blood* / Q000235:genetics
C486563:BCL11A protein, human; D002352:Carrier Proteins; D018840:HSP70 Heat-Shock Proteins; D009687:Nuclear Proteins; D020626:Oncogene Proteins v-myb; D010445:Peptide Elongation Factors; D012097:Repressor Proteins; D005319:Fetal Hemoglobin; D019204:GTP-Binding Proteins; C000628258:HBS1L protein, human
Fetal hemoglobin; Quantitative trait loci; Zhuang population; β-Thalassemia intermedia