![]() ![]() Globulin levels were calculated as the difference between total protein and albumin. Total serum protein and serum albumin were measured on an ADIVA1650 (Siemens, Tarrytown, NY, USA) and analyzed at a commercial analytical service center (SCL Co., Seoul, Korea). Written informed consent was obtained from all participants, and this research project was approved by the institutional review board of the Korea National Institute of Health. The Ansung cohort comprised 4205 persons and was the validation data set for the replication study. The Ansan cohort consisted of 4637 individuals and was used as the discovery data set for GWAS. ![]() Participants were recruited from residents in two cities (Ansung and Ansan) in Gyeonggi-do province, Korea. Study subjects were selected from an ongoing population-based cohort, as part of the Korean Genome and Epidemiology Study. ![]() 9, 10, 11 Thus, we performed a GWAS using two population-based cohorts, comprising 8842 Korean individuals. 7, 8 Previous GWASs have reported candidate genes for total serum proteins, serum albumin and globulins, but A/G ratio was not considered the target phenotype. Recent genome-wide association studies (GWASs) have identified many loci that are linked to common diseases and quantitative traits. 3 A low A/G ratio is associated with all-cause mortality after non-ST (electrocardiogram S and T wave interval) elevation myocardial infarction, 4 nephrotic syndrome 5 and autoimmune disease. 2 This pattern is the classical change that is expected to accompany liver disease when serum albumin decreases below normal levels. 1 The primary clinical manifestation of the A/G ratio is a reduction due to a decrease in serum albumin, and the subsequent increase in serum globulins. The albumin:globulin ratio (A/G ratio) is a biochemical parameter that is used to interpret changes in serum proteins that accompany disease. The other significant signal was observed on chromosome 11q12.2-the FADS1 locus (SNP: rs174548)-with an overall combined P-value=3.54 × 10 −8. ![]() The most compelling association was observed in the TNFRSF13B locus on chromosome 17p11.2 (SNP: rs4561508), with an overall combined P-value=7.80 × 10 −24. Eleven SNPs from six loci ( GALNT2, IRF4, HLA- DBP1, SLC31A1, FADS1 and TNFRSF13B) were replicated, with P-values<0.05. These 38 signals were tested in the Ansung population. From the GWAS of the Ansan cohort, we identified two significant genome-wide signals ( P-values<5 × 10 −8) and 36 moderate signals ( P-value<1.0 × 10 −4). Genetic factors for A/G ratio were analyzed by linear regression analysis, controlling for age, sex, body mass index, smoking status and alcohol drinking status as covariates. The single-nucleotide polymorphism (SNP) genotypes of Affymetrix SNP array 5.0 were obtained from the Korean Association Resource Consortium, and we selected 290 659 common SNPs with a minor allele frequency >0.05. To identify the genetic basis of the A/G ratio, we performed a GWAS on A/G ratio in 4205 individuals from the Ansan cohort and confirmed the results in 4637 subjects from the Ansung cohort. Genome-wide association studies (GWASs) have been identifying genetic variants associated with total serum protein, serum albumin and globulins, but A/G ratio has never been considered the target phenotype. Low albumin:globulin (A/G) ratios are associated with vascular adverse events, nephrotic syndrome and autoimmune disease. ![]()
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