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Association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

ABSTRACT: BACKGROUND:Increased levels of fetal hemoglobin (HbF) can improve the clinical course of the patients with sickle cell anemia (SCA) or ?-thalassemia. The HBG1-HBD intergenic region plays an important role in this process. However, very few studies investigated whether the variations in this region have an effect on HbF expression. METHODS:We retrieved all the SNP data in the HBG1-HBD intergenic region and defined the haplotype blocks, then performed cluster analysis and selected a tagSNP. A total of 500 normal individuals and 300 ?-thalassemia carriers were enrolled. After routine blood and hemoglobin capillary electrophoresis testing, ?-thalassemia mutations were detected using PCR-reverse dot blot. The genotypes of the rs4910736 (A > C) and rs10128556 (C > T) were determined using Sanger sequencing; the relationship between the two SNPs and the levels of HbF was analyzed. RESULTS:Two haplotype blocks were constructed. Block 1 included seven haplotypes divided into two groups M and N by 11 tagSNPs, among which rs4910736 was selected as a tagSNP, while block 2 included three haplotypes. We found that the haplotypes of block 1 were statistically associated with HbF levels, but the non-tagSNP rs10128556 was shown to be more strongly associated with HbF levels than rs4910736. CONCLUSION:This work proved that the haplotypes in the HBG1-HBD intergenic region and SNP rs10128556 are both statistically associated with HbF levels, revealing the association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

SUBMITTER: Hu L

PROVIDER: S-EPMC7307336 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

Hu Li L Huang Ling L Han Yuanyuan Y Jin Tingting T Liu Juan J Jiang Minmin M Liu Xingmei X Li Yuanyuan Y Han Wenping W An Bangquan B Huang Shengwen S

Journal of clinical laboratory analysis 20200218 6

<h4>Background</h4>Increased levels of fetal hemoglobin (HbF) can improve the clinical course of the patients with sickle cell anemia (SCA) or β-thalassemia. The HBG1-HBD intergenic region plays an important role in this process. However, very few studies investigated whether the variations in this region have an effect on HbF expression.<h4>Methods</h4>We retrieved all the SNP data in the HBG1-HBD intergenic region and defined the haplotype blocks, then performed cluster analysis and selected a ...[more]

PMID: 32068918

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Project description:Behçet's disease (BD) susceptibility had been associated with single-nucleotide polymorphisms (SNPs) in IL23R-IL12RB2, IL10, STAT4, or ERAP1 locus in Japanese, Turkish, Chinese, and other populations, but not in a Korean genome-wide association study (GWAS). We aimed to fine-map BD risk association of these four loci using extensive imputation and additional genotyping for replication.In the discovery phase, 369 patients with BD enrolled in the previous Korean GWAS and 2000 controls retrieved from a population-based cohort of healthy Koreans were imputed for their genotypes of all SNPs in the four loci using the Asian data of the 1000 Genomes Project as reference. For genotype imputation of ERAP1 SNPs, the adjacent ERAP2 SNPs were also covered. For the 10 most significantly associated SNPs (8 imputed and 2 GWAS-genotyped), an additional 84 patients with BD and 283 healthy controls were genotyped for replication. The results from the discovery and replication phases were pooled for meta-analysis using the Mantel-Haenszel test to estimate the odds ratio (OR) and 95% confidence interval (CI).An IL23R-IL12RB2 intergenic SNP rs1495965 was significantly associated with BD risk (OR (95% CI)?=?1.5 (1.3, 1.7), P?=?2.5?×?10-7) in the pooled meta-analysis of the discovery (1.4 (1.2, 1.7), P?=?4.9?×?10-7) and replication (1.9 (1.3, 2.6), P?=?6.0?×?10-4) phases. BD risk association was fine-mapped on the intergenic region rather than the two flanking genes, as rs1495966 and rs4655535, almost perfectly correlated with rs1495965 (r 2?=?0.99), were also located in the same intergenic region. Consistent with previous reports, the P values tended to be lower within IL23R than IL12RB2. On the other hand, several IL10 SNPs were suggested for association in the discovery phase but all failed in the replication phase. No SNP in ERAP1-ERAP2 and STAT4 was suggested even in the discovery phase.BD susceptibility association was fine-mapped on the intergenic region between IL23R and IL12RB2 as marked by three correlated SNPs, rs1495965, rs1495966, and rs4655535.

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Dataset Information

Association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

Publications

Association of polymorphisms in the HBG1-HBD intergenic region with HbF levels.

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