FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1969766197> ?p ?o ?g. }

• W1969766197 endingPage "159" @default.
• W1969766197 startingPage "156" @default.
• W1969766197 abstract "We read with interest the recently published article entitled, ‘Sickle cell disease in Saudi Arabia: the phenotype in adults with the Arab-Indian haplotype is not benign' (Alsultan et al, 2014). The authors showed that adults with sickle cell disease (SCD) from the Eastern province of Saudi Arabia present with severe clinical complications in spite of the presence of the much-believed mild Arab-Indian haplotype and high fetal haemoglobin (HbF) levels. SCD has the most complex pathophysiology and incredibly diverse clinical presentation (Kutlar, 2007). Many genetic factors, such as high HbF levels, Xmn-I polymorphism (HBG2:g.-158C>T), β-globin gene (HBB) haplotype and α-thalassaemia, are known to ameliorate the clinical severity of the disease. However, none of these can fully explain the differences in clinical expression observed in these patients (Kutlar, 2007; Colah et al, 2014). Earlier studies have shown that SCD is also milder in Indians, being linked to the Arab-Indian haplotype (Kar et al, 1986; Mukherjee et al, 1997). However clinical variability was noted between tribal and non-tribal populations (Mukherjee et al, 1997; Colah et al, 2014). A recent retrospective analysis of 316 children with SCD in central India showed that 30% of them had severe disease (Jain et al, 2012). Here we have analysed our data and reviewed the medical records of 110 adult patients [sickle homozygous (SS)-80, sickle-β-thalassaemia (S-β-thal)-30] (aged 13–55 years) from western and central India who were either hospitalized or attended clinics. This work was approved by the Ethical Committee of the National Institute of Immunohaematology. Seventy-five percent of the SS patients and 77% of S-β-thal patients were clinically severe despite having the Arab-Indian haplotype (Table 1). Repeated vaso-occlusive crises (VOC) followed by frequent hospitalizations for severe crisis or infections and severe anaemia requiring blood transfusions were most commonly seen among the patients classified as severe. Ten patients had a history of stroke. Avascular necrosis of the femur (AVNF) was mostly seen after the age of 15 years. 73·5% of our sickle homozygous patients with splenomegaly (3–7 cm) were between 13 and 20 years of age. Molecular analysis for confirmation of the sickle, β and α-genotypes, β-cluster haplotype and the Xmn-I polymorphism was performed as described earlier (Italia et al, 2009). Among the sickle-β-thalassaemia patients, four severe β-thalassaemia mutations were seen {HBB:c.92+5G>C [IVS 1-5(G→C)] – 24, HBB:c.47G>A [codon 15(G→A)] – 4, HBB:c.126_129delCTTT [codon 41/42(-CTTT)] – 1, HBB:c.51delC [codon 16(-C)] – 1}. The MTHFR (C677T) and VCAM1 (G1238C) polymorphisms were also analysed as they have been shown to be predictive markers for vascular complications and stroke in patients with SCD (Adekile et al, 2001; Taylor et al, 2002). The Xmn-I polymorphism was present (+/+) in 95% of severe SS patients who had the Arab-Indian haplotype. 28·3% of severe SS patients had α-thalassaemia compared with 50% of patients with a milder presentation. There was no difference in the prevalence of α-thalassaemia in the two groups of patients. The MTHFR C677T polymorphism was found in 13·1% of patients with severe clinical manifestations as compared to 18·1% in patients with a milder presentation. In the severe SCD patients, those with MTHFR (−/−) had an average of 3–5 VOC/year as compared to patients with MTHFR (+/−) and (+/+) who had an average of 5–8 VOC/year. However, this difference in VOC was not statistically significant. Of the 10 patients with a history of stroke, 9 (6-SS and 3-S-thal) were MTHFR (−/−) whereas one HbS-β-thalassaemia patient (7·7%) was MTHFR (+/+). There was no difference in the occurrence of other clinical complications among patients with different MTHFR polymorphisms. VCAM1 G1238C polymorphism was not seen in our SCD patients or in the 80 normal adults studied. The risk of stroke is considered to be 300-fold in children with sickle cell anaemia. Several studies have shown associations between certain single nucleotide polymorphisms (SNPs) and the risk of vascular disease and stroke. However, none of the SNPs have been universally proved to be predictive markers for these complications (Adekile et al, 2001; Kutlar, 2007). The presence of the MTHFR C677T polymorphism in our population showed no statistically significant association between VOC and stroke. Taylor et al (2002) studied variants in the VCAM1 gene to correlate these with the risk of stroke in SCD. The VCAM1 G1238 allele was more common in patients who had a stroke compared to the control group, suggesting a protective role of the C variant against stroke. However, in our study, the G1238 allele was present in all the cases. The haematological findings are shown in Table 2. HbS and HbF levels were measured by high performance liquid chromatography and F-cells were enumerated by flow cytometry (Italia et al, 2009). The Hb and the HbF levels were slightly higher in the milder groups of SCD patients. Steinberg et al (2014) recently suggested that the concentration of HbF/F-cells should be approximately 9–12 pg for HbF to be protective or for inhibiting HbS from polymerizing. 19·3% of our severe SCD patients had a concentration of HbF/F-cells above 9 pg compared to 40·7% of milder patients (P < 0·01). Eighty-three of our adult SCD patients (75·4%) had a severe clinical presentation. Our study may have overestimated the prevalence of complications, similar to the report by Alsultan et al (2014), as we analysed only those patients who attended clinics or were hospitalized. However, we also show that a large proportion of adult SCD patients in India have a severe clinical presentation. Greater awareness and improved medical facilities in rural areas will probably reduce mortality but will also bring more SCD patients to medical attention. Our study showed that the phenotype of SCD in adults with the Arab-Indian haplotype among Indians is quite diverse with both severe and milder manifestation in subgroups of patients. This work was supported by the Indian Council of Medical Research, New Delhi. RC designed the research study. KI and HK performed the research, KI, AHN and RC analysed the data. KI wrote the paper, CSC and KG performed the clinical follow-up of the patients and RC and KG critically reviewed the paper. The authors have nothing to disclose. There are no conflicts of interest to declare." @default.
• W1969766197 created "2016-06-24" @default.
• W1969766197 creator A5007775762 @default.
• W1969766197 creator A5017913326 @default.
• W1969766197 creator A5031782697 @default.
• W1969766197 creator A5032744996 @default.
• W1969766197 creator A5059146350 @default.
• W1969766197 creator A5073378889 @default.
• W1969766197 date "2014-08-19" @default.
• W1969766197 modified "2023-09-27" @default.
• W1969766197 title "Variable phenotypes of sickle cell disease in India with the Arab-Indian haplotype" @default.
• W1969766197 cites W2002718117 @default.
• W1969766197 cites W2003821284 @default.
• W1969766197 cites W2023346445 @default.
• W1969766197 cites W2047089057 @default.
• W1969766197 cites W2056214346 @default.
• W1969766197 cites W2064693159 @default.
• W1969766197 cites W2073274964 @default.
• W1969766197 cites W2106601506 @default.
• W1969766197 cites W2155090266 @default.
• W1969766197 cites W2171378832 @default.
• W1969766197 doi "https://doi.org/10.1111/bjh.13083" @default.
• W1969766197 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/25135424" @default.
• W1969766197 hasPublicationYear "2014" @default.
• W1969766197 type Work @default.
• W1969766197 sameAs 1969766197 @default.
• W1969766197 citedByCount "15" @default.
• W1969766197 countsByYear W19697661972015 @default.
• W1969766197 countsByYear W19697661972016 @default.
• W1969766197 countsByYear W19697661972018 @default.
• W1969766197 countsByYear W19697661972019 @default.
• W1969766197 countsByYear W19697661972020 @default.
• W1969766197 countsByYear W19697661972021 @default.
• W1969766197 countsByYear W19697661972022 @default.
• W1969766197 crossrefType "journal-article" @default.
• W1969766197 hasAuthorship W1969766197A5007775762 @default.
• W1969766197 hasAuthorship W1969766197A5017913326 @default.
• W1969766197 hasAuthorship W1969766197A5031782697 @default.
• W1969766197 hasAuthorship W1969766197A5032744996 @default.
• W1969766197 hasAuthorship W1969766197A5059146350 @default.
• W1969766197 hasAuthorship W1969766197A5073378889 @default.
• W1969766197 hasConcept C104317684 @default.
• W1969766197 hasConcept C126322002 @default.
• W1969766197 hasConcept C127716648 @default.
• W1969766197 hasConcept C135763542 @default.
• W1969766197 hasConcept C197754878 @default.
• W1969766197 hasConcept C2779134260 @default.
• W1969766197 hasConcept C54355233 @default.
• W1969766197 hasConcept C71924100 @default.
• W1969766197 hasConcept C86803240 @default.
• W1969766197 hasConceptScore W1969766197C104317684 @default.
• W1969766197 hasConceptScore W1969766197C126322002 @default.
• W1969766197 hasConceptScore W1969766197C127716648 @default.
• W1969766197 hasConceptScore W1969766197C135763542 @default.
• W1969766197 hasConceptScore W1969766197C197754878 @default.
• W1969766197 hasConceptScore W1969766197C2779134260 @default.
• W1969766197 hasConceptScore W1969766197C54355233 @default.
• W1969766197 hasConceptScore W1969766197C71924100 @default.
• W1969766197 hasConceptScore W1969766197C86803240 @default.
• W1969766197 hasIssue "1" @default.
• W1969766197 hasLocation W19697661971 @default.
• W1969766197 hasLocation W19697661972 @default.
• W1969766197 hasOpenAccess W1969766197 @default.
• W1969766197 hasPrimaryLocation W19697661971 @default.
• W1969766197 hasRelatedWork W1828691184 @default.
• W1969766197 hasRelatedWork W1965396974 @default.
• W1969766197 hasRelatedWork W1981169569 @default.
• W1969766197 hasRelatedWork W1983642025 @default.
• W1969766197 hasRelatedWork W1998686087 @default.
• W1969766197 hasRelatedWork W2002128513 @default.
• W1969766197 hasRelatedWork W2013158704 @default.
• W1969766197 hasRelatedWork W2038331681 @default.
• W1969766197 hasRelatedWork W2066137273 @default.
• W1969766197 hasRelatedWork W2092874662 @default.
• W1969766197 hasVolume "168" @default.
• W1969766197 isParatext "false" @default.
• W1969766197 isRetracted "false" @default.
• W1969766197 magId "1969766197" @default.
• W1969766197 workType "article" @default.