Influence of blood group, Glucose-6-phosphate dehydrogenase and Haemoglobin genotype on Falciparum malaria in children in Vihiga highland of Western Kenya.
- 作者列表："Ahmed JS","Guyah B","Sang' D","Webale MK","Mufyongo NS","Munde E","Ouma C
BACKGROUND:Genetic diversity of ABO blood, glucose-6-phosphate dehydrogenase (G6PD) deficiency and haemoglobin type and their ability to protect against malaria vary geographically, ethnically and racially. No study has been carried out in populations resident in malaria regions in western Kenya. METHOD:A total of 574 malaria cases (severe malaria anaemia, SMA = 137 and non-SMA = 437) seeking treatment at Vihiga County and Referral Hospital in western Kenya, were enrolled and screened for ABO blood group, G6PD deficiency and haemoglobin genotyped in a hospital-based cross-sectional study. RESULT:When compared to blood group O, blood groups A, AB and B were not associated with SMA (P = 0.380, P = 0.183 and P = 0.464, respectively). Further regression analysis revealed that the carriage of the intermediate status of G6PD was associated with risk to SMA (OR = 1.52, 95%CI = 1.029-2.266, P = 0.035). There was, however, no association between AS and SS with severe malaria anaemia. Co-occurrence of both haemoglobin type and G6PD i.e. the AA/intermediate was associated with risk to SMA (OR = 1.536, 95%CI = 1.007-2.343, P = 0.046) while the carriage of the AS/normal G6PD was associated with protection against SMA (OR = 0.337, 95%CI = 0.156-0.915, P = 0.031). CONCLUSION:Results demonstrate that blood group genotypes do not have influence on malaria disease outcome in this region. Children in Vihiga with blood group O have some protection against malaria. However, the intermediate status of G6PD is associated with risk of SMA. Further, co-inheritance of sickle cell and G6PD status are important predictors of malaria disease outcome. This implies combinatorial gene function in influencing disease outcome.
背景: ABO血液、葡萄糖-6-磷酸脱氢酶 (G6PD) 缺乏症和血红蛋白类型的遗传多样性及其预防疟疾的能力在地域、种族和种族上各不相同。没有在肯尼亚西部疟疾地区的居民中进行研究。 方法: 共纳入574例疟疾病例 (重度疟疾贫血，sma137 = 437，非sma= =)，在肯尼亚西部的维希加县和转诊医院寻求治疗，并进行ABO血型筛查，g6PD缺乏症和血红蛋白基因分型在医院为基础的横断面研究。 结果: 与o型血相比，A、AB和B型血与SMA无相关性 (分别为p = 0.380、p = 0.183和p = 0.464)。进一步的回归分析显示，G6PD中间状态的携带与SMA风险相关 (or = 1.52，1.029 ci = 2.266-0.035，p =)。然而，AS和SS与严重疟疾贫血之间没有关联。同时出现血红蛋白类型和G6PD，即。AA/中间体与SMA风险相关 (or = 1.536 ci = 1.007-2.343，p = 0.046)，而携带AS/正常G6PD与SMA保护相关 (or = 0.337 ci = 0.156-0.915，P = 0.031)。 结论: 血型基因型对本地区疟疾疾病转归无影响。Vihiga血型为O的儿童对疟疾有一定的保护作用。然而，G6PD的中间状态与SMA的风险相关。此外，镰状细胞和G6PD状态的共遗传是疟疾疾病结果的重要预测因子。这意味着组合基因在影响疾病结果中的功能。
METHODS:BACKGROUND:Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE:In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN:In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS:As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION:Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.
METHODS:OBJECTIVES:Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN:In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS:We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION:Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.
METHODS:OBJECTIVES:Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS:The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS:A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS:We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.