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Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus

Klannemark, Mia LU ; Suurinkeroinen, L; Orho-Melander, Marju LU ; Groop, Leif LU and Taskinen, M R (2000) In Diabetic Medicine 17(8). p.599-605
Abstract
AIMS: Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes. METHODS: The subjects were... (More)
AIMS: Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes. METHODS: The subjects were genotyped with an allele-specific mini-sequencing method. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. RESULTS: The frequency of the Asn/Ser genotype was significantly increased in normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/1), and was associated with dyslipidaemia and increased systolic blood pressure. There was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in Asn/ Ser carriers with reduced insulin sensitivity. The frequency of the Asn/Ser genotype was not increased in diabetic subjects with hypertriglyceridaemia, but was associated with increased systolic blood pressure. CONCLUSIONS: The Asn/Ser genotype of the LPL gene is associated with dyslipidaemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin-resistant subjects. This association is not seen in diabetic subjects. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Diabetic Medicine
volume
17
issue
8
pages
599 - 605
publisher
Wiley-Blackwell
external identifiers
  • pmid:11073182
  • scopus:0033819075
ISSN
1464-5491
DOI
10.1046/j.1464-5491.2000.00343.x
language
English
LU publication?
yes
id
0fd865a6-f9b0-46cc-95b5-1f6a9d94eeb3 (old id 1118052)
date added to LUP
2008-06-24 13:57:32
date last changed
2017-06-04 04:15:56
@article{0fd865a6-f9b0-46cc-95b5-1f6a9d94eeb3,
  abstract     = {AIMS: Lipoprotein lipase (LPL) is a major regulator of triglyceride clearance. A genetic variant of the LPL gene on chromosome 8p22, Asn291Ser, has previously been associated with dyslipidaemia and an increased frequency of cardiovascular disease as well as familial disorders of lipoprotein metabolism. The aim of this study was to test whether the phenotypic expression of the LPL Asn291Ser variant is dependent upon glucose tolerance and insulin resistance. Therefore, the Asn291Ser variant was examined in 192 patients with Type 2 diabetes, 278 subjects with normal glucose tolerance who are first degree relatives of patients with Type 2 diabetes and 226 healthy control spouses without family history of diabetes. METHODS: The subjects were genotyped with an allele-specific mini-sequencing method. Insulin resistance was estimated using the homeostasis model assessment (HOMA) index. RESULTS: The frequency of the Asn/Ser genotype was significantly increased in normoglycaemic subjects with hypertriglyceridaemia (> 1.7 mmol/1), and was associated with dyslipidaemia and increased systolic blood pressure. There was a significant interaction between Asn291Ser and insulin resistance in normoglycaemic subjects, indicating that dyslipidaemia is more severe in Asn/ Ser carriers with reduced insulin sensitivity. The frequency of the Asn/Ser genotype was not increased in diabetic subjects with hypertriglyceridaemia, but was associated with increased systolic blood pressure. CONCLUSIONS: The Asn/Ser genotype of the LPL gene is associated with dyslipidaemia in normoglycaemic subjects, and the dyslipidaemic phenotype is more severe in insulin-resistant subjects. This association is not seen in diabetic subjects.},
  author       = {Klannemark, Mia and Suurinkeroinen, L and Orho-Melander, Marju and Groop, Leif and Taskinen, M R},
  issn         = {1464-5491},
  language     = {eng},
  number       = {8},
  pages        = {599--605},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetic Medicine},
  title        = {Interaction between the Asn291Ser variant of the LPL gene and insulin resistance on dyslipidaemia in high risk individuals for Type 2 diabetes mellitus},
  url          = {http://dx.doi.org/10.1046/j.1464-5491.2000.00343.x},
  volume       = {17},
  year         = {2000},
}