Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Obesity is strongly implicated in the pathophysiology of insulin resistance, diabetes mellitus and dyslipidemia. The mechanisms, however, by which obesity causes these complications are not known. The study of single-gene disorders affecting adipose tissue may elucidate some of the mechanisms involved in these processes. Familial partial lipodystrophy, Dunnigan variety, (FPLD, OMIM 308980) is an autosomal-dominant condition characterized by marked loss of subcutaneous adipose tissue affecting the trunk and extremities but with excess fat deposition in the head and neck areas. Affected individuals show an increased preponderance of insulin resistance, diabetes mellitus, dyslipidemia and acanthosis nigricans. The genetic basis of FPLD is unknown. We carried out a genome-wide scan with a set of highly polymorphic short tandem-repeats (STR) in individuals from five well-characterized pedigrees and mapped the FPLD locus to chromosome 1q21-22. The maximum two-point lod score obtained with a highly polymorphic microsatellite at D1S2624 at theta(max)=0 was 5.84. Multipoint-linkage analysis yielded a peak lod score of 8.25 between D1S305 and D1S1600. There was no evidence for genetic heterogeneity (alpha=1) in the pedigrees.
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PMID:Localization of the gene for familial partial lipodystrophy (Dunnigan variety) to chromosome 1q21-22. 950 May 56

Familial partial lipodystrophy, Dunnigan type (FPLD; Mendelian Inheritance in Man #151660), is an autosomal dominant disorder characterized by loss of s.c. fat from the extremities and trunk since puberty and predisposition to insulin resistance and its complications. However, for lack of recognition of affected men, previous studies could not ascertain any gender differences in phenotypic expression. Therefore, anthropometric variables and prevalence of diabetes mellitus, dyslipidemia, hypertension, and atherosclerotic vascular disease were compared among 17 postpubertal men and 22 women with FPLD from eight pedigrees. All individuals completed a questionnaire, and fasting blood was analyzed for glucose, insulin, and lipoprotein concentrations. Both affected men and women had similar patterns of fat loss. Compared with the affected men, women had higher prevalence of diabetes (18% and 50%, respectively; P = 0.05) and atherosclerotic vascular disease (12% and 45%, respectively; P = 0.04) and had higher serum triglycerides (median values, 2.27 and 4.25 mmol/L, respectively; P = 0.02) and lower high-density lipoprotein cholesterol concentrations (age-adjusted means, 0.94 and 0.70 mmol/L, respectively; P = 0.04). The prevalence of hypertension and fasting serum insulin concentrations were similar. In conclusion, women with FPLD are more severely affected with metabolic complications of insulin resistance than men. These observations raise the possibility that women with generalized and regional obesity may also have more severe metabolic sequelae of insulin resistance.
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PMID:Gender differences in the prevalence of metabolic complications in familial partial lipodystrophy (Dunnigan variety). 1084 51

The common syndrome of insulin resistance is frequently seen in obese individuals, and is characterized by glucose intolerance, dyslipidemia, high blood pressure, and an increased risk of coronary heart disease. A rare genetic form of insulin resistance is Dunnigan-type familial partial lipodystrophy (FPLD; OMIM #151660), which is characterized by loss of subcutaneous fat from extremities, trunk, and gluteal region, and always by insulin resistance and hyperinsulinemia, often with hypertension, dyslipidemia, type-2 diabetes and early endpoints of atherosclerosis. FPLD was recently discovered to result from mutated LMNA (R482Q; OMIM #150330.0010), which is the gene encoding nuclear lamins A and C. Results from extended pedigrees indicate that dyslipidemia precedes the plasma glucose abnormalities in FPLD subjects with mutant LMNA, and that the hyperinsulinemia is present early in the course of the disease. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. Thus, rare mutations in a nuclear structural protein can be associated with markedly abnormal qualitative and quantitative phenotypes, indicating that a defect in the structure and function of the nuclear envelope can result in a phenotype that shares many aspects with the common syndrome of insulin resistance.
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PMID:Insulin resistance in human partial lipodystrophy. 1112 71

Dunnigan-type familial partial lipodystrophy (FPLD; OMIM 151660) is a rare monogenic form of insulin resistance characterized by loss of subcutaneous fat from the extremities, trunk, and gluteal region. FPLD recapitulates the main metabolic attributes of the insulin resistance syndrome, including central obesity, hyperinsulinemia, glucose intolerance and diabetes, dyslipidemia, and hypertension. Through the use of focused DNA sequencing of positional candidate genes on chromosome 1q21, we discovered that FPLD results from mutations in LMNA (R482Q; OMIM 150330.0010), which is the gene that encodes nuclear lamins A and C. By stratifying members of extended FPLD pedigrees according to LMNA genotype, we found that hyperinsulinemia is present early in the course of the disease and that dyslipidemia (characterized by high triglycerides and depressed HDL cholesterol) precedes the development of glucose abnormalities. Plasma leptin is also markedly reduced in subjects with FPLD due to mutant LMNA. The findings in FPLD indicate that defective structure of the nuclear envelope produces a phenotype of insulin resistance. The findings may have relevance for common insulin resistance and for drug-associated lipodystrophies, whose molecular basis is unknown at present.
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PMID:Familial partial lipodystrophy: a monogenic form of the insulin resistance syndrome. 1113 44