scholarly journals Genome-Wide Association Study (GWAS) on Bilirubin Concentrations in Subjects with Metabolic Syndrome: Sex-Specific GWAS Analysis and Gene-Diet Interactions in a Mediterranean Population

Nutrients ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 90 ◽  
Author(s):  
Oscar Coltell ◽  
Eva M. Asensio ◽  
José V. Sorlí ◽  
Rocio Barragán ◽  
Rebeca Fernández-Carrión ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Serum Bilirubin ◽  
Total Serum Bilirubin ◽  
Genome Wide Association ◽  
Total Serum ◽  
Mediterranean Population ◽  
Gender Perspective ◽  
Men And Women ◽  
Major Locus ◽  
Genome Wide

Although, for decades, increased serum bilirubin concentrations were considered a threatening sign of underlying liver disease and had been associated with neonatal jaundice, data from recent years show that bilirubin is a powerful antioxidant and suggest that slightly increased serum bilirubin concentrations are protective against oxidative stress-related diseases, such as cardiovascular diseases. Therefore, a better understanding of the gene-diet interactions in determining serum bilirubin concentrations is needed. None of the previous genome-wide association studies (GWAS) on bilirubin concentrations has been stratified by sex. Therefore, considering the increasing interest in incorporating the gender perspective into nutritional genomics, our main aim was to carry out a GWAS on total serum bilirubin concentrations in a Mediterranean population with metabolic syndrome, stratified by sex. Our secondary aim was to explore, as a pilot study, the presence of gene-diet interactions at the GWAS level. We included 430 participants (188 men and 242 women, aged 55–75 years, and with metabolic syndrome) in the PREDIMED Plus-Valencia study. Global and sex-specific GWAS were undertaken to analyze associations and gene-diet interaction on total serum bilirubin. Adherence (low and high) to the Mediterranean diet (MedDiet) was analyzed as the dietary modulator. In the GWAS, we detected more than 55 SNPs associated with serum bilirubin at p < 5 × 10−8 (GWAS level). The top-ranked were four SNPs (rs4148325 (p = 9.25 × 10−24), rs4148324 (p = 9.48 × 10−24), rs6742078 (p = 1.29 × 10−23), rs887829 (p = 1.39 × 10−23), and the rs4148324 (p = 9.48 × 10−24)) in the UGT1A1 (UDP glucuronosyltransferase family 1 member A1) gene, which replicated previous findings revealing the UGT1A1 as the major locus. In the sex-specific GWAS, the top-ranked SNPs at the GWAS level were similar in men and women (the lead SNP was the rs4148324-UGT1A1 in both men (p = 4.77 × 10−11) and women (p = 2.15 × 10−14), which shows homogeneous genetic results for the major locus. There was more sex-specific heterogeneity for other minor genes associated at the suggestive level of GWAS significance (p < 1 × 10−5). We did not detect any gene-MedDiet interaction at p < 1 × 10−5 for the major genetic locus, but we detected some gene-MedDiet interactions with other genes at p < 1 × 10−5, and even at the GWAS level for the IL17B gene (p = 3.14 × 10−8). These interaction results, however, should be interpreted with caution due to our small sample size. In conclusion, our study provides new data, with a gender perspective, on genes associated with total serum bilirubin concentrations in men and women, and suggests possible additional modulations by adherence to MedDiet.

scholarly journals Genome-wide association meta-analysis for total serum bilirubin levels

2009 ◽  
Vol 18 (14) ◽  
pp. 2700-2710 ◽  
Author(s):  
A. D. Johnson ◽  
M. Kavousi ◽  
A. V. Smith ◽  
M.-H. Chen ◽  
A. Dehghan ◽  
...  
Keyword(s):  
Serum Bilirubin ◽  
Meta Analysis ◽  
Total Serum Bilirubin ◽  
Genome Wide Association ◽  
Total Serum ◽  
Genome Wide

Two Different UGT1A1 Mutations causing Crigler–Najjar Syndrome types I and II in an Iranian Family

2015 ◽  
Vol 24 (4) ◽  
pp. 523-526 ◽  
Author(s):  
Yoshihiro Maruo ◽  
Mahdiyeh Behnam ◽  
Shinichi Ikushiro ◽  
Sayuri Nakahara ◽  
Narges Nouri ◽  
...  
Keyword(s):  
Serum Bilirubin ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Compound Heterozygous ◽  
Type I ◽  
Syndrome Type ◽  
Type Ii ◽  
Wild Type ◽  
Iranian Family ◽  
Udp Glucuronosyltransferase

Background: Crigler–Najjar syndrome type I (CN-1) and type II (CN-2) are rare hereditary unconjugated hyperbilirubinemia disorders. However, there have been no reports regarding the co-existence of CN-1 and CN-2 in one family. We experienced a case of an Iranian family that included members with either CN-1 or CN-2. Genetic analysis revealed a mutation in the bilirubin UDP-glucuronosyltransferase (UGT1A1) gene that resulted in residual enzymatic activity.Case report: The female proband developed severe hyperbilirubinemia [total serum bilirubin concentration (TB) = 34.8 mg/dL] with bilirubin encephalopathy (kernicterus) and died after liver transplantation. Her family history included a cousin with kernicterus (TB = 30.0 mg/dL) diagnosed as CN-1. Her great grandfather (TB unknown) and uncle (TB = 23.0 mg/dL) developed jaundice, but without any treatment, they remained healthy as CN-2. Results: The affected cousin was homozygous for a novel frameshift mutation (c.381insGG, p.C127WfsX23). The affected uncle was compound heterozygous for p.C127WfsX23 and p.V225G linked with A(TA)7TAA. p.V225G-UGT1A1 reduced glucuronidation activity to 60% of wild-type. Thus, linkage of A(TA)7TAA and p.V225G might reduce UGT1A1 activity to 18%–36 % of the wild-type. Conclusion: Genetic and in vitro expression analyses are useful for accurate genetic counseling for a family with a history of both CN-1 and CN-2. Abbreviations: CN-1: Crigler–Najjar syndrome type I; CN-2: Crigler–Najjar syndrome type II; GS: Gilbert syndrome; UGT1A1: bilirubin UDP-glucuronosyltransferase; WT: Wild type; TB: total serum bilirubin.

Genome-Wide Association and Transcriptome Analysis Reveals Total Serum Ghrelin to Be Linked with GFRAL

2020 ◽  
Author(s):  
Dirk Alexander Wittekind ◽  
Markus Scholz ◽  
Jürgen Kratzsch ◽  
Markus Loeffler ◽  
Katrin Horn ◽  
...  
Keyword(s):  
Transcriptome Analysis ◽  
Genome Wide Association ◽  
Total Serum ◽  
Genome Wide ◽  
Serum Ghrelin

scholarly journals Genome-wide association analysis of metabolic syndrome quantitative traits in the GENNID multiethnic family study

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Jia Y. Wan ◽  
Deborah L. Goodman ◽  
Emileigh L. Willems ◽  
Alexis R. Freedland ◽  
Trina M. Norden-Krichmar ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Family Study ◽  
Genome Wide Association ◽  
European American ◽  
Japanese American ◽  
Genetic Associations ◽  
Chromosome 11 ◽  
Genome Wide ◽  
American Families

Abstract Background To identify genetic associations of quantitative metabolic syndrome (MetS) traits and characterize heterogeneity across ethnic groups. Methods Data was collected from GENetics of Noninsulin dependent Diabetes Mellitus (GENNID), a multiethnic resource of Type 2 diabetic families and included 1520 subjects in 259 African-American, European-American, Japanese-Americans, and Mexican-American families. We focused on eight MetS traits: weight, waist circumference, systolic and diastolic blood pressure, high-density lipoprotein, triglycerides, fasting glucose, and insulin. Using genotyped and imputed data from Illumina’s Multiethnic array, we conducted genome-wide association analyses with linear mixed models for all ethnicities, except for the smaller Japanese-American group, where we used additive genetic models with gene-dropping. Results Findings included ethnic-specific genetic associations and heterogeneity across ethnicities. Most significant associations were outside our candidate linkage regions and were coincident within a gene or intergenic region, with two exceptions in European-American families: (a) within previously identified linkage region on chromosome 2, two significant GLI2-TFCP2L1 associations with weight, and (b) one chromosome 11 variant near CADM1-LINC00900 with pleiotropic blood pressure effects. Conclusions This multiethnic family study found genetic heterogeneity and coincident associations (with one case of pleiotropy), highlighting the importance of including diverse populations in genetic research and illustrating the complex genetic architecture underlying MetS.

scholarly journals Transcutaneous billirubinometry to estimate total serum bilirubin in neonatal jaundice

2017 ◽  
Vol 57 (1) ◽  
pp. 8 ◽  
Author(s):  
Andra Kurnianto ◽  
Herman Bermawi ◽  
Afifa Darmawanti ◽  
Erial Bahar
Keyword(s):  
Neonatal Jaundice ◽  
Serum Bilirubin ◽  
Subcutaneous Tissue ◽  
Correlation Coefficients ◽  
Total Serum Bilirubin ◽  
Blood Sampling ◽  
Total Serum ◽  
Transcutaneous Bilirubin ◽  
Non Invasive ◽  
Transcutaneous Bilirubinometry

Background The gold standard for diagnosis of neonatal jaundice is total serum bilirubin (TSB) measurement. This method, however, is invasive, painful, and costly in terms of workload, time, and money. Moreover, repeated blood sampling may lead to significant blood loss, which is of particular concern in preterm infants. To overcome these drawbacks, non-invasive methods of bilirubin measurement have been proposed. Transcutaneous bilirubinometry (TcB) determines the yellowness of the subcutaneous tissue of a newborn infant by measuring the difference between optical densities for light in the blue and green wavelength regions.Objective To evaluate the accuracy of transcutaneous bilirubinometry for estimating TSB levels in neonatal jaundice.Methods Subjects were infants aged < 28 days with jaundice who had never been treated with phototherapy or exchange transfusion. The study was done from February to July 2016 in Mohammad Hoesin Hospital. Subjects underwent transcutaneous bilirubin (TcB) and TSB assays, with a maximum interval of 15 minutes between tests.Results One hundred fifty patients were included in this study. The TcB values > 5 mg/dL were correlated to TSB > 5 mg/dL, with 100% sensitivity and 83.3% specificity. This cut-off point was obtained from a receiver-operator characteristic (ROC) curve with AUC 99.3% (95%CI 97.9 to 100%; P< 0.001).The correlation coefficients (r) for TSB and TcB measurements on the forehead were 0.897 (P<0.001).Conclusion Transcutaneous bilirubinometry can be used to accurately estimate TSB levels in neonatal jaundice, and may be useful in clinical practice as a non-invasive method to reduce blood sampling.

scholarly journals Development of Jaundice Detection Approaches in Neonates

2020 ◽  
Vol 22 (12) ◽  
Author(s):  
Priti Bhagat V ◽  
◽  
Dr Mukesh Raghuwanshi M ◽  
Dr. Kavita Singh ◽  
Dr Sachin Damke ◽  
...  
Keyword(s):  
Clinical Assessment ◽  
Serum Bilirubin ◽  
Visual Assessment ◽  
Assessment Methods ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Gold Standard Method ◽  
Life Detection ◽  
Precision And Accuracy ◽  
Transcutaneous Bilirubinometer

Jaundice is one of the most common diseases that have a significant impact in the first few days of newborn life. Detection and regular monitoring of bilirubin, which is responsible for Jaundice, is an essential phase during the hyperbilirubinemia. In the literature, various clinical assessment methods of Jaundice are available. It motivates us to present a review of these clinical assessment methods in practice, along with their advantages and limitations. In this paper, we have discussed three widely used methods, such as visual assessment, total serum bilirubin and transcutaneous bilirubinometer. From the comparative analysis of these methods, it is concluded that the visual assessment is very subjective in nature, whereas, the total serum bilirubin method is still a gold standard method. The detailed analysis of the methods depicts that the correlation between this two total serum bilirubin and transcutaneous bilirubinometer has enormous potential for improvement resulting in the enhancement in precision and accuracy of bilirubin measurement.

scholarly journals Possible Ibuprofen-Induced Kernicterus in a Near-Term Infant with Moderate Hyperbilirubinemia.

2006 ◽  
Vol 11 (4) ◽  
pp. 245-250
Author(s):  
Peter Gal ◽  
J Laurence Ransom ◽  
Sherri A Davis
Keyword(s):  
Neonatal Intensive Care ◽  
Serum Bilirubin ◽  
Primary Pulmonary Hypertension ◽  
Term Infant ◽  
Auditory Neuropathy ◽  
Total Serum Bilirubin ◽  
Total Serum ◽  
Albumin Binding ◽  
Unbound Bilirubin ◽  
Near Term

A 36-week gestation newborn was admitted to the neonatal intensive care unit for treatment of primary pulmonary hypertension and possible sepsis. The infant developed hyperbilirubinemia on day 4 of life and peaked on day 5 at a total serum bilirubin of 19 mg/dL. Phototherapy was started on day 4 and continued for 5 days. On day 8 of life, ibuprofen was started for fever; a concurrent total serum bilirubin was 15.7 mg/dL. The subsequent hospital course was uneventful, and discharge occurred on day 22 of life. Because the patient failed a hearing screen at discharge, he was referred for a diagnostic audiology workup. He subsequently failed formal audiometric testing on two occasions one week apart, and was given a diagnosis of auditory dys-synchrony and/or auditory neuropathy, consistent with kernicterus. At 5½ months of age, he was reported to be hypotonic and to have frequent arching movements. Since the total serum bilirubin did not exceed 19 mg/dL, concern was raised that ibuprofen may have caused displacement of bilirubin from its albumin binding site, resulting in kernicterus due to excessive unbound bilirubin concentrations. Ibuprofen should be administered with caution in preterm infants at risk for kernicterus.

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