Dataset Information

Genomewide association study of HLA alloimmunization in previously pregnant blood donors.

ABSTRACT: Alloimmunization through blood transfusion, transplantation, or circulating fetal cells during pregnancy is a significant concern. Some exposed individuals make alloantibodies while others do not, implying variation in genetic risk factors.We conducted a genomewide association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to identify genetic variants for HLA alloimmunization in previously pregnant blood donors with (n?=?752) and without (n?=?753) HLA Class I or II alloantibodies.A SNP in the neurexophilin 2 (NXPH2) gene surpassed genome-wide significance (p?=?2.06 × 10-8 ), with multiple adjacent markers p < 10-6 , for women with anti-Class I alloantibodies only. Little is currently known about the function of NXPH2, although gene family members have been shown to impact immunity. SNPs in the E2F7 gene, a transcription factor related to cell cycle control and cellular proliferation, also approached genomewide significance (p?=?2.5 × 10-7 ).Further work to extend the GWAS approach and to characterize variants in NXPH2 and E2F7 in the context of alloantibody formation is warranted.

SUBMITTER: Seielstad M

PROVIDER: S-EPMC5803399 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Genomewide association study of HLA alloimmunization in previously pregnant blood donors.

Seielstad Mark M Page Grier P GP Gaddis Nathan N Lanteri Marion M Lee Tzong-Hae TH Kakaiya Ram R Barcellos Lisa F LF Criswell Lindsey A LA Triulzi Darrell D Norris Philip J PJ Busch Michael P MP

Transfusion 20171122 2

<h4>Background</h4>Alloimmunization through blood transfusion, transplantation, or circulating fetal cells during pregnancy is a significant concern. Some exposed individuals make alloantibodies while others do not, implying variation in genetic risk factors.<h4>Study design and methods</h4>We conducted a genomewide association study (GWAS) of 9,427,497 single-nucleotide polymorphisms (SNPs) to identify genetic variants for HLA alloimmunization in previously pregnant blood donors with (n = 752) ...[more]

PMID: 29168253

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Project description:BACKGROUND:In low and middle-income countries (LMIC), the total and LDL cholesterol and triglyceride levels of residents of urban areas are reported to be higher than those of rural areas. This may be due to differences in lifestyle behaviors between residents of urban areas and rural areas in LMIC. In this study, our aims were to (1) examine whether or not LDL cholesterol, total/HDL ratios and triglyceride levels of individuals in densely populated areas are higher than those of individuals living in less-densely populated areas in a high-income country (HIC) and (2) investigate the potential mediating roles of physical activity and sedentary behavior. METHODS:We used cross-sectional data from 2547 Dutch blood donors that participated in Donor InSight-III. Linear regression was used to analyze the association between population density and LDL cholesterol, total/HDL cholesterol ratio and HDL cholesterol. The mediating roles of moderate-to-vigorous physical activity (MVPA) and sedentary behavior were investigated in a subsample (n?=?740) for which objectively measured MVPA/sedentary behavior data was available. Multiple mediation with linear regression analyses were performed and the product-of-coefficients method was used to calculate direct and indirect effects. RESULTS:Mean LDL cholesterol and median total cholesterol/HDL cholesterol ratio and triglyceride levels were 2.89, 3.43 and 1.29 mmol/L, respectively. Population density was not associated with LDL cholesterol [? 0.00 (- 0.01; 0.01)], log transformed total/HDL cholesterol ratio [? 1.00 (1.00; 1.00)] and triglyceride levels [? 1.00 (0.99; 1.00)]. No statistically significant direct or indirect effects were found. CONCLUSION:Contrary to previous findings in LMIC, no evidence was found that population density is associated with blood lipid levels in blood donors in the Netherlands or that MVPA and sedentary behavior mediate this association. This may be the result of socioeconomic differences and, in part, may be due to the good health of the study population and the relatively high population density in the Netherlands. Also, compared to LMIC, differences in physical activity levels in more versus less populated areas may be less pronounced in HIC.

Dataset Information

Genomewide association study of HLA alloimmunization in previously pregnant blood donors.

Publications

Genomewide association study of HLA alloimmunization in previously pregnant blood donors.

Similar Datasets

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