• Je něco špatně v tomto záznamu ?

Variants influencing age at diagnosis of HNF1A-MODY

AH. Ludwig-Słomczyńska, MT. Seweryn, P. Radkowski, P. Kapusta, J. Machlowska, S. Pruhova, D. Gasperikova, C. Bellanne-Chantelot, A. Hattersley, B. Kandasamy, L. Letourneau-Freiberg, L. Philipson, A. Doria, PP. Wołkow, MT. Małecki, T. Klupa

. 2022 ; 28 (1) : 113. [pub] 20220914

Jazyk angličtina Země Anglie, Velká Británie

Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem

Perzistentní odkaz   https://www.medvik.cz/link/bmc22024413

Grantová podpora
R01 DK104942 NIDDK NIH HHS - United States
P30 DK020595 NIDDK NIH HHS - United States
HHSN268201000029C NHLBI NIH HHS - United States
HHSN261200800001E NCI NIH HHS - United States

BACKGROUND: HNF1A-MODY is a monogenic form of diabetes caused by variants in the HNF1A gene. Different HNF1A variants are associated with differences in age of disease onset, but other factors are postulated to influence this trait. Here, we searched for genetic variants influencing age of HNF1A-MODY onset. METHODS: Blood samples from 843 HNF1A-MODY patients from Czech Republic, France, Poland, Slovakia, the UK and the US were collected. A validation set consisted of 121 patients from the US. We conducted a genome-wide association study in 843 HNF1A-MODY patients. Samples were genotyped using Illumina Human Core arrays. The core analysis was performed using the GENESIS package in R statistical software. Kinship coefficients were estimated with the KING and PC-Relate algorithms. In the linear mixed model, we accounted for year of birth, sex, and location of the HNF1A causative variant. RESULTS: A suggestive association with age of disease onset was observed for rs2305198 (p = 2.09E-07) and rs7079157 (p = 3.96E-06) in the HK1 gene, rs2637248 in the LRMDA gene (p = 2.44E-05), and intergenic variant rs2825115 (p = 2.04E-05). Variant rs2637248 reached nominal significance (p = 0.019), while rs7079157 (p = 0.058) and rs2825115 (p = 0.068) showed suggestive association with age at diabetes onset in the validation set. CONCLUSIONS: rs2637248 in the LRMDA gene is associated with age at diabetes onset in HNF1A-MODY patients.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc22024413
003      
CZ-PrNML
005      
20221031100252.0
007      
ta
008      
221017s2022 enk f 000 0|eng||
009      
AR
024    7_
$a 10.1186/s10020-022-00542-0 $2 doi
035    __
$a (PubMed)36104811
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a enk
100    1_
$a Ludwig-Słomczyńska, Agnieszka H $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland
245    10
$a Variants influencing age at diagnosis of HNF1A-MODY / $c AH. Ludwig-Słomczyńska, MT. Seweryn, P. Radkowski, P. Kapusta, J. Machlowska, S. Pruhova, D. Gasperikova, C. Bellanne-Chantelot, A. Hattersley, B. Kandasamy, L. Letourneau-Freiberg, L. Philipson, A. Doria, PP. Wołkow, MT. Małecki, T. Klupa
520    9_
$a BACKGROUND: HNF1A-MODY is a monogenic form of diabetes caused by variants in the HNF1A gene. Different HNF1A variants are associated with differences in age of disease onset, but other factors are postulated to influence this trait. Here, we searched for genetic variants influencing age of HNF1A-MODY onset. METHODS: Blood samples from 843 HNF1A-MODY patients from Czech Republic, France, Poland, Slovakia, the UK and the US were collected. A validation set consisted of 121 patients from the US. We conducted a genome-wide association study in 843 HNF1A-MODY patients. Samples were genotyped using Illumina Human Core arrays. The core analysis was performed using the GENESIS package in R statistical software. Kinship coefficients were estimated with the KING and PC-Relate algorithms. In the linear mixed model, we accounted for year of birth, sex, and location of the HNF1A causative variant. RESULTS: A suggestive association with age of disease onset was observed for rs2305198 (p = 2.09E-07) and rs7079157 (p = 3.96E-06) in the HK1 gene, rs2637248 in the LRMDA gene (p = 2.44E-05), and intergenic variant rs2825115 (p = 2.04E-05). Variant rs2637248 reached nominal significance (p = 0.019), while rs7079157 (p = 0.058) and rs2825115 (p = 0.068) showed suggestive association with age at diabetes onset in the validation set. CONCLUSIONS: rs2637248 in the LRMDA gene is associated with age at diabetes onset in HNF1A-MODY patients.
650    12
$a diabetes mellitus 2. typu $x diagnóza $x genetika $7 D003924
650    12
$a celogenomová asociační studie $7 D055106
650    _2
$a hepatocytární jaderný faktor 1-alfa $x genetika $7 D051538
650    _2
$a lidé $7 D006801
650    _2
$a fenotyp $7 D010641
655    _2
$a časopisecké články $7 D016428
655    _2
$a Research Support, N.I.H., Extramural $7 D052061
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Seweryn, Michał T $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland $u Department of Pharmacogenomics, The Ohio State University, Columbus, OH, USA
700    1_
$a Radkowski, Piotr $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland
700    1_
$a Kapusta, Przemysław $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland
700    1_
$a Machlowska, Julita $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland
700    1_
$a Pruhova, Stepanka $u Department of Pediatrics, Charles University in Prague, Second Faculty of Medicine and University Hospital Motol, Prague, Czech Republic
700    1_
$a Gasperikova, Daniela $u Institute of Experimental Endocrinology, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovakia
700    1_
$a Bellanne-Chantelot, Christine $u Department of Genetics, Hôpital Pitié-Salpêtrière, Paris, France
700    1_
$a Hattersley, Andrew $u Exeter Medical School, Exeter, UK
700    1_
$a Kandasamy, Balamurugan $u Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
700    1_
$a Letourneau-Freiberg, Lisa $u Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
700    1_
$a Philipson, Louis $u Kovler Diabetes Center, University of Chicago, Chicago, IL, USA
700    1_
$a Doria, Alessandro $u Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA
700    1_
$a Wołkow, Paweł P $u Center For Medical Genomics OMICRON, Jagiellonian University Medical College, Kraków, Poland
700    1_
$a Małecki, Maciej T $u Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland
700    1_
$a Klupa, Tomasz $u Department of Metabolic Diseases, Jagiellonian University Medical College, Kraków, Poland. tomasz.klupa@uj.edu.pl $1 https://orcid.org/0000000271994079
773    0_
$w MED00003396 $t Molecular medicine (Cambridge, Mass. Print) $x 1528-3658 $g Roč. 28, č. 1 (2022), s. 113
856    41
$u https://pubmed.ncbi.nlm.nih.gov/36104811 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20221017 $b ABA008
991    __
$a 20221031100249 $b ABA008
999    __
$a ok $b bmc $g 1854240 $s 1175703
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2022 $b 28 $c 1 $d 113 $e 20220914 $i 1528-3658 $m Molecular medicine (Cambridge, Mass. Print) $n Mol Med $x MED00003396
GRA    __
$a R01 DK104942 $p NIDDK NIH HHS $2 United States
GRA    __
$a P30 DK020595 $p NIDDK NIH HHS $2 United States
GRA    __
$a HHSN268201000029C $p NHLBI NIH HHS $2 United States
GRA    __
$a HHSN261200800001E $p NCI NIH HHS $2 United States
LZP    __
$a Pubmed-20221017
Zpět

Najít záznam

Citační ukazatele

Možnosti archivace