An LMNA variant is associated with dyslipidemia and insulin resistance in the Japanese.
Nuclear lamins A and C are encoded by LMNA and are present in terminally differentiated cells. Rare mutations in LMNA were shown to cause familial partial lipodystrophy, a syndrome characterized by regional loss of adipose tissue, glucose intolerance, and dyslipidemia, making LMNA a candidate gene for insulin-resistant diabetes. The aim of this study was to investigate whether genetic variation in LMNA can influence the risk of type 2 diabetes in a Japanese cohort. First, we performed mutational screening of LMNA by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and sequence analysis in 8 insulin-resistant males with acanthosis nigricans who were not lipodystrophic. One known single nucleotide polymorphism, 1908C/T, was found in exon 10. We subsequently screened samples of 171 nondiabetic and 164 type 2 diabetic male subjects for the presence of the 1908C/T polymorphism by PCR-restriction fragment length polymorphism (RFLP). The frequency of subjects with the 1908T allele tended to be higher in the diabetic group than in the nondiabetic group; however, the difference was not significant (43.9% v 32.2%) (P =.084). Carriers of the 1908T allele, both among diabetics and nondiabetics, showed significantly higher fasting insulin, triglycerides (TG), total cholesterol (TC), and lower high-density lipoprotein-cholesterol (HDL-C) levels than those of the 1908C/C subjects. These results suggest the LMNA 1908C/T single nucleotide polymorphism (SNP) is not associated with the prevalence of type 2 diabetes, although it may be a factor predisposing to insulin resistance and dyslipidemia in some Japanese.
Murase
Yuko
Y
Second Department of Internal Medicine, Kanazawa University, Ishikawa, Japan.
Yagi
Kunimasa
K
Katsuda
Yuko
Y
Asano
Akimichi
A
Koizumi
Junji
J
Mabuchi
Hiroshi
H
D000328:Adult; D000368:Aged; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D007564:Japan / Q000453:epidemiology; D034882:Lamins; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence
D034882:Lamins; D009687:Nuclear Proteins