Bhanushali Aparna A, Himani Kumari, Patra Pradeep K, Das Bibhu R
a Research and Development, SRL Ltd. , Goregaon (W), Mumbai , India.
b Department of Biochemistry , Pandit Jawaharlal Nehru Memorial Medical College , Raipur , Chhattisgarh , India.
Hemoglobin. 2017 Jul-Nov;41(4-6):317-320. doi: 10.1080/03630269.2017.1414059.
The prevalence of sickle cell disease in India is very high. Hb F is one of the most powerful modulators of disease severity in sickle cell disease patients. It was traditionally thought that the disease is milder in Indian sickle cell disease patients predominantly due to the Arab-Indian haplotype characterized by the HBG XmnI [rs7482144 (G>A)] variant, which is associated with increased Hb F levels. In the current study, we investigated the Hb F levels in individuals with the rs10128556 (C>T) variant and also determined its linkage with the HBG XmnI variant. The present study was conducted on a cohort of 275 individuals, which consisted of 221 patients with sickle cell disease and 54 patients with sickle cell trait. Analysis of hemoglobin (Hb) fractions and variants was done on the high performance liquid chromatography (HPLC) system. Genotyping for rs10128556 was done by direct sequencing of the products. Mean Hb F levels in the sickle cell disease patients was 19.36 ± 6.79. The genotypic frequencies for rs10128556 were 82.0% (TT), 16.7% (CT) and 1.3% (CC) for sickle cell disease patients. The minor C allele resulted in 52.0% decrease in Hb F levels when homozygous and 7.0% decrease when heterozygous. The rs10128556 single nucleotide polymorphism (SNP) was in strong but not complete linkage with the HBG XmnI variant. In conclusion, the study determined for the first time the frequency and association of rs10128556 in Indian sickle cell disease patients with Hb F. It also established that it was not in complete linkage with the HBG XmnI variant in this high risk population.
镰状细胞病在印度的患病率非常高。胎儿血红蛋白（Hb F）是镰状细胞病患者疾病严重程度最有力的调节因子之一。传统上认为，印度镰状细胞病患者的病情较轻，主要是由于以胎儿血红蛋白γ基因（HBG）XmnI [rs7482144 (G>A)] 变体为特征的阿拉伯 - 印度单倍型，该变体与胎儿血红蛋白水平升高有关。在本研究中，我们调查了携带rs10128556 (C>T) 变体个体的胎儿血红蛋白水平，并确定了其与胎儿血红蛋白γ基因XmnI变体的连锁关系。本研究针对275名个体组成的队列进行，其中包括221名镰状细胞病患者和54名镰状细胞性状患者。在高效液相色谱（HPLC）系统上进行血红蛋白（Hb）组分和变体分析。通过对产物进行直接测序对rs10128556进行基因分型。镰状细胞病患者的平均胎儿血红蛋白水平为19.36±6.79。镰状细胞病患者中rs10128556的基因型频率为82.0%（TT）、16.7%（CT）和1.3%（CC）。纯合时，次要的C等位基因导致胎儿血红蛋白水平降低52.0%，杂合时降低7.0%。rs10128556单核苷酸多态性（SNP）与胎儿血红蛋白γ基因XmnI变体存在强连锁但不完全连锁。总之，该研究首次确定了rs10128556在印度镰状细胞病患者中与胎儿血红蛋白的频率及关联。研究还证实，在这一高风险人群中，它与胎儿血红蛋白γ基因XmnI变体并非完全连锁。
