1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet
Modeling the course of C-peptide decline in autoantibody (Ab) positive individuals is important for type 1 diabetes (T1D) prediction and implementation of T1D prevention trials. Single nucleotide polymorphisms in TCF7L2, JAZF1, SLC30A8, INS, PTPRK, G6CP2, CLEC16, PTPN22 and HLA genes are associated...
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| Veröffentlicht in: | Diabetes (New York, N.Y.) N.Y.), 2022-06, Vol.71 (Supplement_1) |
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| creator | TRIOLO, TAYLOR M. PARIKH, HEMANG M. TOSUR, MUSTAFA GOTTLIEB, PETER ORAM, RICHARD A. ONENGUT-GUMUSCU, SUNA KRISCHER, JEFFREY RICH, STEPHEN S. STECK, ANDREA REDONDO, MARIA J. |
| description | Modeling the course of C-peptide decline in autoantibody (Ab) positive individuals is important for type 1 diabetes (T1D) prediction and implementation of T1D prevention trials. Single nucleotide polymorphisms in TCF7L2, JAZF1, SLC30A8, INS, PTPRK, G6CP2, CLEC16, PTPN22 and HLA genes are associated with persistent C-peptide at or after T1D diagnosis. We sought to determine whether 12 SNPs in these genes and the T1D genetic risk score-2 (GRS2) can predict C-peptide trajectory before diagnosis of T1D. We studied Ab positive at-risk participants in the TrialNet Pathway to Prevention Study who had ImmunoChip data (N=1217, age at initial screen (mean±SD) 16.1±12.7 years, 51.5% female, 81.0% non-Hispanic white) . Over a mean follow up of 3.4±2. years, 255 (21.0%) developed multiple Ab and 336 (27.6%) developed clinical T1D. We analyzed the influence of these 12 SNPs and the T1D GRS2 on C-peptide AUC during progression from single to multiple Abs, from single Ab to clinical T1D, and from multiple Abs to clinical T1D. Analyses were adjusted for baseline C-peptide AUC, age, glucose AUC, BMI Z-score and HbA1c; the presence of high-risk HLA haplotypes (DR3 and DR4-DQ8) ; and the first 3 principal components. The type 2 diabetes (T2D) -associated TCF7L2 rs7901695 and rs4506565 SNPs were significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p |
| doi_str_mv | 10.2337/db22-1254-P |
| format | Article |
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In conclusion, T2D-associated SNPs in the TCF7L2 gene and lower T1D GRS2 predict higher C-peptide particularly in progression from multiple Abs to clinical T1D.</description><identifier>ISSN: 0012-1797</identifier><identifier>EISSN: 1939-327X</identifier><identifier>DOI: 10.2337/db22-1254-P</identifier><language>eng</language><publisher>New York: American Diabetes Association</publisher><subject>Autoantibodies ; Clinical trials ; Diabetes ; Diabetes mellitus (insulin dependent) ; Diabetes mellitus (non-insulin dependent) ; Diagnosis ; Haplotypes ; Histocompatibility antigen HLA ; Medical diagnosis ; Peptides ; Protein-tyrosine-phosphatase ; Single-nucleotide polymorphism</subject><ispartof>Diabetes (New York, N.Y.), 2022-06, Vol.71 (Supplement_1)</ispartof><rights>Copyright American Diabetes Association Jun 2022</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>TRIOLO, TAYLOR M.</creatorcontrib><creatorcontrib>PARIKH, HEMANG M.</creatorcontrib><creatorcontrib>TOSUR, MUSTAFA</creatorcontrib><creatorcontrib>GOTTLIEB, PETER</creatorcontrib><creatorcontrib>ORAM, RICHARD A.</creatorcontrib><creatorcontrib>ONENGUT-GUMUSCU, SUNA</creatorcontrib><creatorcontrib>KRISCHER, JEFFREY</creatorcontrib><creatorcontrib>RICH, STEPHEN S.</creatorcontrib><creatorcontrib>STECK, ANDREA</creatorcontrib><creatorcontrib>REDONDO, MARIA J.</creatorcontrib><title>1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet</title><title>Diabetes (New York, N.Y.)</title><description>Modeling the course of C-peptide decline in autoantibody (Ab) positive individuals is important for type 1 diabetes (T1D) prediction and implementation of T1D prevention trials. Single nucleotide polymorphisms in TCF7L2, JAZF1, SLC30A8, INS, PTPRK, G6CP2, CLEC16, PTPN22 and HLA genes are associated with persistent C-peptide at or after T1D diagnosis. We sought to determine whether 12 SNPs in these genes and the T1D genetic risk score-2 (GRS2) can predict C-peptide trajectory before diagnosis of T1D. We studied Ab positive at-risk participants in the TrialNet Pathway to Prevention Study who had ImmunoChip data (N=1217, age at initial screen (mean±SD) 16.1±12.7 years, 51.5% female, 81.0% non-Hispanic white) . Over a mean follow up of 3.4±2. years, 255 (21.0%) developed multiple Ab and 336 (27.6%) developed clinical T1D. We analyzed the influence of these 12 SNPs and the T1D GRS2 on C-peptide AUC during progression from single to multiple Abs, from single Ab to clinical T1D, and from multiple Abs to clinical T1D. Analyses were adjusted for baseline C-peptide AUC, age, glucose AUC, BMI Z-score and HbA1c; the presence of high-risk HLA haplotypes (DR3 and DR4-DQ8) ; and the first 3 principal components. The type 2 diabetes (T2D) -associated TCF7L2 rs7901695 and rs4506565 SNPs were significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p<0.04) and neared significance for the single-to-multiple Ab transition (p=0.05) . Additionally, lower T1D GRS2 was significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p=0.01) . We observed trend associations of lower C-peptide AUC with JAZF1 SNP rs864745 in both single Ab-to-T1D and multiple Ab-to-T1D progression (both p=0.06) , and with SNPs in SLC30A8 and INS in multiple Abs to T1D (p=0.and 0.08, respectively) .
In conclusion, T2D-associated SNPs in the TCF7L2 gene and lower T1D GRS2 predict higher C-peptide particularly in progression from multiple Abs to clinical T1D.</description><subject>Autoantibodies</subject><subject>Clinical trials</subject><subject>Diabetes</subject><subject>Diabetes mellitus (insulin dependent)</subject><subject>Diabetes mellitus (non-insulin dependent)</subject><subject>Diagnosis</subject><subject>Haplotypes</subject><subject>Histocompatibility antigen HLA</subject><subject>Medical diagnosis</subject><subject>Peptides</subject><subject>Protein-tyrosine-phosphatase</subject><subject>Single-nucleotide polymorphism</subject><issn>0012-1797</issn><issn>1939-327X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><recordid>eNotkD9PwzAQxS0EEqUw8QUsMSKD_yR2zIYKFKQKMmRgs2LnglyVONjp0G-PQ9ENd-_up3fSQ-ia0TsuhLrvLOeE8bIg9QlaMC00EVx9nqIFpSxflFbn6CKlLaVU5logc6Qf8BoGmLzDdYTOu8mHAYcer0gN4-Q7wE1st-CmEA_YQh9i3hxGwAw_-dbCBGkevoaQfMJ-yLhvd-8wXaKzvt0luPrvS9S8PDerV7L5WL-tHjfEyYIRJbhmVSG0VEBlZzWbtdQCNLRSVE5V3BVF1Xe0r4CVQpbgrNW263QJIMQS3Rxtxxh-9pAmsw37OOSPhsuqLLObYJm6PVIuhpQi9GaM_ruNB8OomQM0c4B_kZha_AI2hGD0</recordid><startdate>20220601</startdate><enddate>20220601</enddate><creator>TRIOLO, TAYLOR M.</creator><creator>PARIKH, HEMANG M.</creator><creator>TOSUR, MUSTAFA</creator><creator>GOTTLIEB, PETER</creator><creator>ORAM, RICHARD A.</creator><creator>ONENGUT-GUMUSCU, SUNA</creator><creator>KRISCHER, JEFFREY</creator><creator>RICH, STEPHEN S.</creator><creator>STECK, ANDREA</creator><creator>REDONDO, MARIA J.</creator><general>American Diabetes Association</general><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope></search><sort><creationdate>20220601</creationdate><title>1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet</title><author>TRIOLO, TAYLOR M. ; PARIKH, HEMANG M. ; TOSUR, MUSTAFA ; GOTTLIEB, PETER ; ORAM, RICHARD A. ; ONENGUT-GUMUSCU, SUNA ; KRISCHER, JEFFREY ; RICH, STEPHEN S. ; STECK, ANDREA ; REDONDO, MARIA J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c641-73291843967e06db912918693e9ea638c782c448fd0f8e15365ecbb9bdd95ee33</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Autoantibodies</topic><topic>Clinical trials</topic><topic>Diabetes</topic><topic>Diabetes mellitus (insulin dependent)</topic><topic>Diabetes mellitus (non-insulin dependent)</topic><topic>Diagnosis</topic><topic>Haplotypes</topic><topic>Histocompatibility antigen HLA</topic><topic>Medical diagnosis</topic><topic>Peptides</topic><topic>Protein-tyrosine-phosphatase</topic><topic>Single-nucleotide polymorphism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>TRIOLO, TAYLOR M.</creatorcontrib><creatorcontrib>PARIKH, HEMANG M.</creatorcontrib><creatorcontrib>TOSUR, MUSTAFA</creatorcontrib><creatorcontrib>GOTTLIEB, PETER</creatorcontrib><creatorcontrib>ORAM, RICHARD A.</creatorcontrib><creatorcontrib>ONENGUT-GUMUSCU, SUNA</creatorcontrib><creatorcontrib>KRISCHER, JEFFREY</creatorcontrib><creatorcontrib>RICH, STEPHEN S.</creatorcontrib><creatorcontrib>STECK, ANDREA</creatorcontrib><creatorcontrib>REDONDO, MARIA J.</creatorcontrib><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><jtitle>Diabetes (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>TRIOLO, TAYLOR M.</au><au>PARIKH, HEMANG M.</au><au>TOSUR, MUSTAFA</au><au>GOTTLIEB, PETER</au><au>ORAM, RICHARD A.</au><au>ONENGUT-GUMUSCU, SUNA</au><au>KRISCHER, JEFFREY</au><au>RICH, STEPHEN S.</au><au>STECK, ANDREA</au><au>REDONDO, MARIA J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet</atitle><jtitle>Diabetes (New York, N.Y.)</jtitle><date>2022-06-01</date><risdate>2022</risdate><volume>71</volume><issue>Supplement_1</issue><issn>0012-1797</issn><eissn>1939-327X</eissn><abstract>Modeling the course of C-peptide decline in autoantibody (Ab) positive individuals is important for type 1 diabetes (T1D) prediction and implementation of T1D prevention trials. Single nucleotide polymorphisms in TCF7L2, JAZF1, SLC30A8, INS, PTPRK, G6CP2, CLEC16, PTPN22 and HLA genes are associated with persistent C-peptide at or after T1D diagnosis. We sought to determine whether 12 SNPs in these genes and the T1D genetic risk score-2 (GRS2) can predict C-peptide trajectory before diagnosis of T1D. We studied Ab positive at-risk participants in the TrialNet Pathway to Prevention Study who had ImmunoChip data (N=1217, age at initial screen (mean±SD) 16.1±12.7 years, 51.5% female, 81.0% non-Hispanic white) . Over a mean follow up of 3.4±2. years, 255 (21.0%) developed multiple Ab and 336 (27.6%) developed clinical T1D. We analyzed the influence of these 12 SNPs and the T1D GRS2 on C-peptide AUC during progression from single to multiple Abs, from single Ab to clinical T1D, and from multiple Abs to clinical T1D. Analyses were adjusted for baseline C-peptide AUC, age, glucose AUC, BMI Z-score and HbA1c; the presence of high-risk HLA haplotypes (DR3 and DR4-DQ8) ; and the first 3 principal components. The type 2 diabetes (T2D) -associated TCF7L2 rs7901695 and rs4506565 SNPs were significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p<0.04) and neared significance for the single-to-multiple Ab transition (p=0.05) . Additionally, lower T1D GRS2 was significantly associated with higher C-peptide AUC during progression from multiple Abs to T1D (p=0.01) . We observed trend associations of lower C-peptide AUC with JAZF1 SNP rs864745 in both single Ab-to-T1D and multiple Ab-to-T1D progression (both p=0.06) , and with SNPs in SLC30A8 and INS in multiple Abs to T1D (p=0.and 0.08, respectively) .
In conclusion, T2D-associated SNPs in the TCF7L2 gene and lower T1D GRS2 predict higher C-peptide particularly in progression from multiple Abs to clinical T1D.</abstract><cop>New York</cop><pub>American Diabetes Association</pub><doi>10.2337/db22-1254-P</doi></addata></record> |
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| subjects | Autoantibodies Clinical trials Diabetes Diabetes mellitus (insulin dependent) Diabetes mellitus (non-insulin dependent) Diagnosis Haplotypes Histocompatibility antigen HLA Medical diagnosis Peptides Protein-tyrosine-phosphatase Single-nucleotide polymorphism |
| title | 1254-P: Genetic Prediction of C-Peptide Trajectory before Type 1 Diabetes Diagnosis in TrialNet |
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