{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T06:54:03Z","timestamp":1789714443149,"version":"4.0.1"},"reference-count":28,"publisher":"American Diabetes Association","issue":"9","content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:p>OBJECTIVE\u2014 Loss of lipin 1 activity causes lipodystrophy and insulin resistance in the fld mouse, and LPIN1 expression and common genetic variation were recently suggested to influence adiposity and insulin sensitivity in humans. We aimed to conduct a comprehensive association study to clarify the influence of common LPIN1 variation on adiposity and insulin sensitivity in U.K. populations and to examine the role of LPIN1 mutations in insulin resistance syndromes.<\/jats:p>\n               <jats:p>RESEARCH DESIGN AND METHOD\u2014 Twenty-two single nucleotide polymorphisms tagging common LPIN1 variation were genotyped in Medical Research Council (MRC) Ely (n = 1,709) and Hertfordshire (n = 2,901) population-based cohorts. LPIN1 exons, exon\/intron boundaries, and 3\u2032 untranslated region were sequenced in 158 patients with idiopathic severe insulin resistance (including 23 lipodystrophic patients) and 48 control subjects.<\/jats:p>\n               <jats:p>RESULTS\u2014 We found no association between LPIN1 single nucleotide polymorphisms and fasting insulin but report a nominal association between rs13412852 and BMI (P = 0.042) in a meta-analysis of 8,504 samples from in-house and publicly available studies. Three rare nonsynonymous variants (A353T, R552K, and G582R) were detected in severely insulin-resistant patients. However, these did not cosegregate with disease in affected families, and Lipin1 protein expression and phosphorylation in patients with variants were indistinguishable from those in control subjects.<\/jats:p>\n               <jats:p>CONCLUSIONS\u2014 Our data do not support a major effect of common LPIN1 variation on metabolic traits and suggest that mutations in LPIN1 are not a common cause of lipodystrophy in humans. The nominal associations with BMI and other metabolic traits in U.K. cohorts require replication in larger cohorts.<\/jats:p>","DOI":"10.2337\/db08-0422","type":"journal-article","created":{"date-parts":[[2008,7,1]],"date-time":"2008-07-01T00:45:07Z","timestamp":1214873107000},"page":"2527-2533","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":42,"title":["Evaluating the Role of <i>LPIN1<\/i> Variation in Insulin Resistance, Body Weight, and Human Lipodystrophy in U.K. Populations"],"prefix":"10.2337","volume":"57","author":[{"given":"Katherine A.","family":"Fawcett","sequence":"first","affiliation":[{"name":"Metabolic Disease Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil","family":"Grimsey","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth J.F.","family":"Loos","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor","family":"Wheeler","sequence":"additional","affiliation":[{"name":"Metabolic Disease Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allan","family":"Daly","sequence":"additional","affiliation":[{"name":"Metabolic Disease Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Soos","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Semple","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Holly","family":"Syddall","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Resource Centre, University of Southampton, Southampton, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cyrus","family":"Cooper","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Resource Centre, University of Southampton, Southampton, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Symeon","family":"Siniossoglou","sequence":"additional","affiliation":[{"name":"Cambridge Institute for Medical Research, University of Cambridge, Wellcome Trust, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen","family":"O'Rahilly","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Addenbrooke's Hospital, University of Cambridge, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas J.","family":"Wareham","sequence":"additional","affiliation":[{"name":"Medical Research Council Epidemiology Unit, Institute of Metabolic Science, Cambridge, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ine\u0302s","family":"Barroso","sequence":"additional","affiliation":[{"name":"Metabolic Disease Group, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031210124971700_R1","doi-asserted-by":"crossref","unstructured":"Peterfy M, Phan J, Xu P, Reue K: Lipodystrophy in the fld mouse results from mutation of a new gene encoding a nuclear protein, lipin. 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