scholarly journals Single Nucleotide Polymorphisms in BCO1 and CD36 Are Related to Macular Pigment Among Children (OR05-04-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Ruyu Liu ◽  
Bridget Hannon ◽  
Katie Robinson ◽  
Lauren Raine ◽  
Billy Hammond ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Single Nucleotide Polymorphisms ◽  
Beta Carotene ◽  
Macular Pigment ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Ancestry Informative Markers ◽  
Single Nucleotide ◽  
Funding Sources ◽  
Heterochromatic Flicker Photometry

Abstract Objectives Xanthophyll carotenoids in the retina have been linked to visual and cognitive health. While genetic variations in genes related to carotenoid cleavage (e.g., beta-carotene-15,15′-monooxygenase [BCO1/BCMO1]) and xanthophyll transport (e.g., Cluster Determinant 36 [CD36]) proteins have been shown to influence MPOD in adults, it is unknown whether these relationships are evident in childhood. We examined the influence of genetic variation (single nucleotide polymorphisms [SNPs]) in BCO1 and CD36 on MPOD in 7–10 year-olds (N = 134). Methods Macular pigment optical density (MPOD) was assessed using heterochromatic flicker photometry. DNA was extracted from saliva samples and genotyped for six tag-selected SNPs, identified by previous work among adults. Ancestry informative markers (AIMs) were genotyped to account for ethnic heterogeneity. Dietary lutein and zeaxanthin (L + Z) was assessed using 3d food records among a subsample (N = 82). Results Minor allele frequencies of BCO1-rs7501331 (T), CD36-rs1527483 (T), CD36-rs3173798 (C) were 0.194, 0.090 and 0.213, respectively. In the partially adjusted (AIMs, age, sex, BMI %tile) models, three of the six SNPs were associated with MPOD. Carriers of the BCO1-rs7501331 T allele had significantly lower (∼18%) MPOD than the CC homozygotes (P = 0.042). Minor allele (T) carriers of CD36-rs1527483 exhibited lower MPOD (∼23%) than CC homozygotes (P = 0.043). CD36-rs3173798 C allele carriers had ∼32% lower MPOD than those with the TT genotype (P < 0.001). Applying the fully adjusted models (AIMs, age, sex, BMI %tile, L + Z) among the subsample revealed that L + Z was a significant predictor of MPOD (P = 0.04); however, CD36-rs3173798 was the only SNP associated with MPOD (P = 0.009). Conclusions MPOD in children is influenced by individual genetic variation. Specifically, variation in the CD36 gene, responsible for a protein involved in transport of lipids and carotenoids, was robustly associated with macular pigment in children. These findings have implications for future recommendations for dietary or supplemental approaches to improving xanthophyll status among children. Funding Sources NIH (HD069381); Abbott Nutrition (2012-04608). iTOPP (2011-67001-30101). USDA AFRI (2015-68001-23248) and the Department of Human Development and Family Studies.

scholarly journals OR24-05 Identifying Regulatory Elements Within a Novel Enhancer of FSHB Containing Two PCOS-Associated Single Nucleotide Polymorphisms

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Stephanie C Bohaczuk ◽  
Varykina G Thackray ◽  
Pamela L Mellon
Keyword(s):  
Transcription Factor ◽  
Single Nucleotide Polymorphisms ◽  
Regulatory Elements ◽  
Minor Allele ◽  
Specific Marker ◽  
Genome Wide Association Studies ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Alcoholic Fatty Liver ◽  
Conserved Region

Abstract Polycystic ovary syndrome (PCOS) is the most common cause of female infertility, affecting approximately 10 percent of women by Rotterdam criteria, and is comorbid with obesity, type II diabetes, hypertension, and non-alcoholic fatty liver disease. As twin studies reveal that genetics account for approximately 70% of PCOS risk, genome-wide association studies (GWAS) can provide powerful insight into PCOS etiology. PCOS GWAS studies from several populations identified a risk locus containing the FSHB gene, which encodes the beta subunit of follicle-stimulating hormone (FSH). As FSH supplementation can restore ovulation in some PCOS patients, deficient FSH signaling could be a causative factor of anovulation and potentially other facets of PCOS. Two of the lead single nucleotide polymorphisms (SNPs) in association with PCOS, rs11031005 and rs11031006, fall within a highly conserved genomic region in mammals. We hypothesized that the conserved region (~450 base pairs) enhances FSHB transcription, and that one or both PCOS-related SNPs alter its function. We have shown that the conserved region from both human and mouse can act as an enhancer of FSHB in LβT2 cells, an immortalized, mouse-derived, mature pituitary gonadotrope cell line, and that its function is altered by the rs11031006 minor allele through modification of an SF1 consensus site. As elimination of the SF1 site reduced but did not completely abolish the function of the enhancer, we continued our investigation to identify additional regulatory sites. Transient transfection of LβT2 cells revealed a possible role for the rs11031005 SNP in FSHB regulation, with the minor allele decreasing enhancer-mediated FSHB transcription. This effect may be due to decreased binding of an unidentified transcription factor, as gel shift revealed that the rs11031005 minor allele reduced the intensity of a binding complex. Using truncations and sliding deletions, we identified three additional putative transcription factor binding sites with consensus sequences for ZEB1, PTX1, and SMAD. To support a role for the conserved region as an enhancer in native chromatin, we assessed the histone status in LβT2 chromatin. Compared to the proximal Fshb promoter, the enhancer-specific marker, H3K4me1, was enriched near the conserved region. Neither promoter/enhancer markers of active (H3K27Ac) or repressed (H3K27me3) chromatin were enriched near the conserved region, although levels of both modifications were consistent with the Fshb proximal promoter. Overall, our data support the role of this conserved region as a novel regulator of FSHB/Fshb transcription and reveal a possible mechanism to explain the contribution of PCOS-associated SNPs through FSHB regulation.

scholarly journals Identification of 1093-bp intron A, SNPS and indels discovered in the porcine pregnancy-associated glycoprotein 2-like (pPAG2-L) gene subfamily in pigs

Genetika ◽  
2020 ◽  
Vol 52 (3) ◽  
pp. 851-866
Author(s):  
Martyna Bieniek-Kobuszewska ◽  
Grzegorz Panasiewicz ◽  
Bożena Szafranska
Keyword(s):  
Genetic Variation ◽  
Single Nucleotide Polymorphisms ◽  
General Knowledge ◽  
Nucleotide Polymorphisms ◽  
Porcine Genome ◽  
Large White ◽  
Bac Clone ◽  
Single Nucleotide ◽  
Noncoding Regions ◽  
Gene Subfamily

The objective of this study was to identify the intron A sequence (between exons 1 and 2) of pPAG2-L, novel single nucleotide polymorphisms (SNPs) and mutations (InDels) within intron A in the crossbreed (Landrace x Large White), Hirshmann hybrid and Duroc pigs. Genomic templates were isolated from leukocytes, amplified, and the gel-out were purified and then sequenced. Positive amplification control included CH242-60C13 BAC clone (Duroc) containing pPAG1-L and pPAG2-L. This is the first report that describes the 1093-bp intron A sequence from the pPAG2-L (Acc. No. KF471015; GenBank), which increased general knowledge of the porcine genome. Novel SNPs/InDels were identified within the intron A of the pPAG2-L in the crossbreeds (72), Duroc (45) and Hirshmann hybrids (17). This is a pioneer study describing identification of the intron A and SNPs/InDels in crossbreeds that provides a novel major pattern that represents a large portion of the genetic variation within the porcine genome. This information should be valuable when genotyping (coding and noncoding regions) multiparous sows from many breeds, in which reproductive phenotypes are known.

Phylogeny and genetic variation in the genus Eranthis using nrITS and cpIS single nucleotide polymorphisms

2019 ◽  
Vol 60 (2) ◽  
pp. 239-252 ◽  
Author(s):  
Seo Young Park ◽  
Mi Jin Jeon ◽  
Sang Hoon Ma ◽  
Eric Wahlsteen ◽  
Keenan Amundsen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Single Nucleotide Polymorphisms ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide

scholarly journals Διαβητική αμφιβληστροειδοπάθεια σε Έλληνες καυκάσιους πάσχοντες από διαβήτη τύπου 2, συσχέτιση με τον πολυμορφισμό στο γονίδιο του αναστολέα του ενεργοποιητή του πλασμινογόνου 1 (ΡAI 1)

2017 ◽  
Author(s):  
Θωμάς Σοκολάκης
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Allele Frequency ◽  
Minor Allele Frequency ◽  
Odds Ratio ◽  
Minor Allele ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Pai 1

Ιστορικό: Υπαρχουν συσσωρεύμενα στοιχεία για την ύπαρξη γενετικής ευαισθησίας στην ανάπτυξη διαβητικής αμφιβληστροειδοπάθειας (ΔΑ). Ο ρόλος του αναστολέα του ενεργοποιητή του πλασμινογόνου-1 (PAI-1) στον κινδυνο αναπτυξης ΔΑ παραμένει αμφιλεγόμενος.Σκοπός: Η παρούσα μελέτη σχεδιάστηκε για να διερευνήσει την πιθανή επίδραση των πολυμορφισμών της περιοχής του γονιδίου PAI-1 στον κίνδυνο ανάπτυξης της ΔΑ και στον κίνδυνο ανάπτυξης ΔΑ πρώιμα έναντι καθυστερημένα κατά τη διάρκεια του σακχαρώδους διαβήτη τύπου 2 (ΣΔ2). Μέθοδοι: Συνολικά 138 ασθενείς με ΔΑ, 107 ασθενείς με ΣΔ2 χωρίς ΔΑ και 315 υγιείς μάρτυρες προσλήφθηκαν. Για να καλυφθεί η πλειοψηφία της γενετικής μεταβλητότητας στην εκτεταμένη περιοχή του γονιδίου ΡΑΙ-1, πέντε πολυμορφισμοί μονού νουκλεοτιδίου (single-nucleotide polymorphisms SNPs) από το HapMap χρησιμοποιώντας μια προσέγγιση ανά ζεύγη και r2> 0,8 και μία μικρή συχνότητα αλληλόμορφων (minor allele frequency MAF)> 0,05 εντοπίστηκαν. Χρησιμοποιώντας αναλύσεις λογιστικής παλινδρόμησης, ετικέτες SNPs και απλότυποι δοκιμάστηκαν για ενώσεις με κίνδυνο ανάπτυξης ΔΑ και με κίνδυνο ανάπτυξης ΔΑ νωρίς ή αργά κατά τη διάρκεια του ΣΔ2. Ο γενικευμένος λόγος πιθανότητας (generalized odds ratio ORG) υπολογίστηκε για την εκτίμηση της επίδρασης μεταλλακτικού φορτίου στην ανάπτυξη ΔΑ μεταξύ όλων των συμμετεχόντων. Διενεργήθηκαν διορθώσεις για πολλαπλές συγκρίσεις (p-τιμή <0,01).Αποτελέσματα: Ένα σημαντικό αποτέλεσμα του rs2070682 στον κίνδυνο πρόωρης έναρξης ΔΑ βρέθηκε στο συνκυριαρχο μοντέλο κληρονομικότητας [αναλογία πιθανότητας, OR (95% διάστημα εμπιστοσύνης, CI): 5.04 (1.47-17.28), p = 0.018]. Ωστόσο, αυτή η σχέση οριακά δεν επιβίωσε πολλαπλών διορθώσεων και δοκιμών. Δεν αποκαλύφθηκε καμία άλλη σημαντική συσχέτιση μεταξύ των επισημάνσεων-SNPs και των απλοτύπων ΡΑΙ-1. Επιπλέον, δεν βρέθηκε σημαντική επίδραση του μεταλλακτικού φορτίου της ετικέττας SNPs στον PAI-1 στον κίνδυνο ανάπτυξης ΔΑ στη διαρκεια του ΣΔ2. Συμπεράσματα: Συμπερασματικά, η παρούσα μελέτη δεν παρέχει καμία ισχυρή απόδειξη ότι οι παραλλαγές του γονιδίου PAI-1 εμπλέκονται στον κίνδυνο ανάπτυξης της ΔΑ ή στην ανάπτυξη της ΔΑ κατά τη διάρκεια του ΣΔ2.

scholarly journals Single nucleotide polymorphisms associated with postoperative inadequate analgesia after single-port VATS in Chinese population

2020 ◽  
Author(s):  
Xiufang Xing ◽  
Yongyu Bai ◽  
Kai Sun ◽  
Min Yan
Keyword(s):  
Single Nucleotide Polymorphisms ◽  
Pain Perception ◽  
Single Port ◽  
Thoracoscopic Surgery ◽  
Clinical Problem ◽  
Minor Allele ◽  
Chinese Patients ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Increased Risk

Abstract Background: Postoperative inadequate analgesia following video-assisted thoracoscopic surgery (VATS) is a common and significant clinical problem. While genetic polymorphisms may play role in the variability of postoperative analgesia effect, few studies have evaluated the associations between genetic mutations and inadequate analgesia after single-port VATS. Methods: Twenty-eight single nucleotide polymorphisms (SNPs) among 18 selected genes involved in pain perception and modulation were genotyped in 198 Chinese patients undergoing single-port VATS. The primary outcome was the occurrence of inadequate analgesia in the first night and morning after surgery which was defined by a comprehensive postoperative evaluation. Multivariable logistic regression analyses were used to identify the association between genetic variations and postoperative inadequate analgesia. Results: The prevalence of postoperative inadequate analgesia was 45.5% in the present study. After controlling for age and education level, association with inadequate analgesia was observed in four SNPs among three genes encoding voltage-gated sodium channels. Patients with the minor allele of rs33985936 (SCN11A), rs6795970 (SCN10A), and 3312G>T (SCN9A) have an increased risk of suffering from inadequate analgesia. While the patients carrying the minor allele of rs11709492 (SCN11A) have lower risk experiencing inadequate analgesia. Conclusions: We identified that SNPs in SCN9A, SCN10A, and SCN11A play a role in the postoperative inadequate analgesia after single-port VATS. Although future larger and long-term follow up studies are warranted to confirm our findings, the results of the current study may be utilized as predictors for forecasting postoperative analgesic effect for patients receiving this type of surgery.Trial registration: This study was retrospectively registered in the ClinicalTrials.gov Registry (NCT03916120) on April 16, 2019.

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