Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India

Meher, Satyabrata; Patel, Siris; Das, Kunal; Dehury, Snehadhini; Jit, Bimal Prasad; Maske, Mahendra M; Das, Padmalaya; Dash, Bisnu Prasad; Mohanty, P.

doi:10.1007/s00277-019-03776-x

Cited by 10 publications

(9 citation statements)

References 48 publications

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“…Homocysteine (Hcy) is one of three sulfur‐containing amino acids in the body and an important intermediate product of the methionine cycle and cysteine metabolism (Abby et al, 1998; Caldeira‐Araujo et al, 2019; Ducker and Rabinowitz, 2017; Meher et al, 2019), which is associated with many diseases, including vascular disease, neurodegenerative disease, and cancer (Min and Min, 2019). 70% to 80% of Hcy exists in the form of plasma proteins; 20% to 30% combines with each other to form dimer Hcy or combines with other thiol compounds to form heterodimers; and another 1% to 2% exists in free form (Ueland, 1995).…”

Section: Introductionmentioning

confidence: 99%

A Cross‐sectional Study on the Relationship Between Homocysteine and Lipid Profiles Among Chinese Population from Hunan

Niu

Chen

Wang

et al. 2020

Lipids

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Previous studies have explored the relationship between homocystein (Hcy) and lipid profiles. However, the results from these studies have been inconsistent. The current study investigated the correlation between Hcy and lipid profiles in Chinese community‐based population. The participants were composed of 4012 Chinese people aged 30–92 years old, who were recruited from rural and urban communities in the Hunan Province. Non‐parametric test and logistic regression were used to examine the distribution of Hcy and lipid profiles (triglyceride [TG], total cholesterol [TC], low‐density lipoprotein cholesterol [LDL‐C], high‐density lipoprotein cholesterol [HDL‐C]) and the relationship between them. The median age of subjects was 54.50 years old, and 40.98% were male. Median Hcy was 13.20 μmol/L, and 35.39% had hyperhomocysteinemia (HHcy). Median TG was 1.51 mmol/L, TC was 4.77 mmol/L, LDL‐C was 2.62 mmol/L, and HDL‐C was 1.27 mmol/L. In multivariable logistic regression analysis, HHcy was associated with high levels of TG (ORmale = 2.240, p < 0.001; ORfemale = 2.539, p < 0.001), TC (ORmale = 2.237, p < 0.001; ORfemale = 2.202, p < 0.001), and LDL‐C (ORmale = 1.413, p = 0.010; ORfemale = 1.617, p < 0.001) in the different sexes population and low level of HDL‐C in females (OR = 1.326, p = 0.023) after adjusting for confounders. HHcy was independently associated with an increasing risk of low HDL‐C among females. The regression analysis showed that HHcy was also associated with hypertriglyceridemia, hypercholesterolemia, and high level of LDL‐C in males and females from Chinese community‐based population, which provides a basis for the treatment and prevention of abnormal lipid metabolism.

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Section: Introductionmentioning

confidence: 99%

A Cross‐sectional Study on the Relationship Between Homocysteine and Lipid Profiles Among Chinese Population from Hunan

Niu

Chen

Wang

et al. 2020

Lipids

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“…With regards to VOC, our meta-analysis found a neutral effect size between SCD children and controls, the wide heterogeneity decreasing after removal of the studies from India [ 29 ] and from Nigeria [ 23 , 24 , 53 ], implying that these latter contributed to the heterogeneity, possibly via the same nutritional and vitamin deficiencies alluded to earlier [ 62 ]. It should be noted that in the VOC comparison, SCD patients were unmatched, preventing the capture of the same genetic, oxidative, and nutritional background of the participants before and after crisis, that might have allowed a better interpretation of the results.…”

Section: Discussionmentioning

confidence: 75%

“…The database search identified 149 citations; as shown in our flowchart ( Figure 1 ), we finally considered 44 articles, 42 of which were full papers [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ] plus one thesis [ 53 ] and one abstract [ 54 ] that examined the relationship between HC, MTHFR, and SCD and that were included in our systematic review and meta-analysis. In particular, Table 1 shows the studies that investigated plasma HC in SCD (22 case-control and 2 cohort studies), Table 2 shows the studies that investigated MTHFR TT and cystathionine beta synthase (all case-control), and Table 3 shows the studies that investigated the MTHFR TT genotype in relation to clinical features of SCD (all cohort studies).…”

Section: Resultsmentioning

confidence: 99%

“…We pooled data from two paediatric [ 12 , 33 ] and six adult studies [ 23 , 24 , 26 , 29 , 32 , 53 ] comprising 249 participants in crisis and 419 unmatched participants in steady state; two studies included patients with IS as part of their VOC, one dealing with children [ 12 ] and one with a mix of children and adults [ 32 ], both from USA. The effect size was neutral with wide heterogeneity ( I 2 = 91.7%, p < 0.0001) ( Supplementary Figure S3A ).…”

Section: Resultsmentioning

confidence: 99%

“…The effect size was neutral with wide heterogeneity ( I 2 = 91.7%, p < 0.0001) ( Supplementary Figure S3A ). After removal of the study from India [ 29 ], the effect size remained neutral with a slightly reduced heterogeneity ( I 2 = 87.1%, p < 0.0001) ( Supplementary Figure S3B ); further removal of the studies from Nigeria [ 23 , 24 , 53 ] shifted effect size to steady state SCD with reduced heterogeneity ( I 2 = 52.7%, p = 0.09) ( Supplementary Figure S3C ).…”

Section: Resultsmentioning

confidence: 99%

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Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis

Arcaro

Caruso²,

Graf

et al. 2022

IJMS

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We evaluated the relevance of plasma homocysteine (HC) and the TT genotype of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism (rs1801133) in sickle cell disease (SCD) and associated vaso-occlusive crisis (VOC) and ischemic stroke (IS). We identified in Embase and Medline 22 studies on plasma HC and 22 on MTHFR genotypes. Due to age-related HC differences, adult and paediatric SCD were separated: 879 adult SCD and 834 controls (CTR) yielded a neutral effect size; 427 paediatric SCD and 625 CTR favoured SCD (p = 0.001) with wide heterogeneity (I2 = 95.5%) and were sub-grouped by country: six studies (Dutch Antilles n = 1, USA n = 5) yielded a neutral effect size, four (India n = 1, Arab countries n = 3) favoured SCD (p < 0.0001). Moreover, 249 SCD in VOC and 419 out of VOC yielded a neutral effect size. The pooled prevalence of the MTHFR TT genotype in 267 SCD equalled that of 1199 CTR (4.26% vs. 2.86%, p = 0.45), and in 84 SCD with IS equalled that of 86 without IS (5.9% vs. 3.7%, p = 0.47); removal of one paediatric study yielded a significant effect size (p = 0.006). Plasma HC in paediatric SCD from Middle East and India was higher, possibly due to vitamin deficiencies. Despite its low prevalence in SCD, the MTHFR TT genotype relates to adult IS.

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Genetic Variation and Sickle Cell Disease Severity

Kirkham,

Estepp,

Weiss

et al. 2023

JAMA Netw Open

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ImportanceSickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.ObjectiveTo assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.Data SourcesPubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.Study SelectionAt least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.Data Extraction and SynthesisData relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.Main Outcomes and MeasuresOutcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.ResultsThe 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10−95 to 6.19 × 10−5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10−7 to 6.00 × 10−4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.Conclusions and RelevanceThe findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.

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Association of plasma homocysteine level with vaso-occlusive crisis in sickle cell anemia patients of Odisha, India

Cited by 10 publications

References 48 publications

A Cross‐sectional Study on the Relationship Between Homocysteine and Lipid Profiles Among Chinese Population from Hunan

A Cross‐sectional Study on the Relationship Between Homocysteine and Lipid Profiles Among Chinese Population from Hunan

Relevance of Plasma Homocysteine and Methylenetetrahydrofolate Reductase 677TT Genotype in Sickle Cell Disease: A Systematic Review and Meta-Analysis

Genetic Variation and Sickle Cell Disease Severity

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