title: Association of the clusterin gene polymorphisms with type 2 diabetes mellitus.
abstract: The association of the clusterin (CLU) gene polymorphism (single nucleotide polymorphisms [SNPs] 1-4: rs1532278, rs1532277, rs2279590, and rs2279591, respectively) with type 2 diabetes mellitus was examined using a population of the Funagata study (n [male-female] = 1631 [741:884]; age, 62.0 ± 12.1 years), a Japanese community-based study. Single nucleotide polymorphisms 1 to 3 were significantly associated with hemoglobin A(1c) levels (P = .0154, .0021, and .0006, respectively) and diabetes (.0310, .0170, and .0021, respectively). A case-control association study of SNP 3 with diabetes by multiple logistic regression analysis showed a significant association of genotype AA (the at-risk genotype) with an odds ratio (OR) of 2.33 (P = .0039) independently of age and sex. The association was marginally validated by a study with another Japanese community-based sample, the Takahata Study (n [male-female] = 2.948 [1333:1615]; age, 63.0 ± 10.2 years) (OR, 1.59; P = .0595; χ(2)P = .0264). When the 2 samples were combined, the association became more significant (OR, 1.75; P = .0025). In subjects with the non-at-risk genotypes, the insulin resistance index--homeostasis model assessment of insulin resistance (HOMA-R)--increased significantly (P < .0001) and the insulin secretion index--HOMA-β--appeared to decrease (P = .1803 and .0097, respectively, for the genotypes AG and GG) as the glucose tolerance progressed toward diabetes (normal glucose tolerance to glucose intolerance to diabetes). However, in subjects with the at-risk genotype, HOMA-R and HOMA-β showed a significant increase already in the subjects with normal glucose tolerance (P = .0239 and .0305, respectively); and as the glucose tolerance progressed toward diabetes, HOMA-R stayed approximately the same, whereas HOMA-β decreased significantly (P = .0332). The CLU gene was associated with diabetes, probably through an increase in insulin resistance primarily and through an impairment of insulin secretion secondarily.
authors.affiliation: Department of Neurology, Hematology, Metabolism, Endocrinology and Diabetology, Yamagata 990-9585, Japan. mdaimon@med.id.yamagata-u.ac.jp
authors.forename: Makoto
authors.initials: M
authors.lastname: Daimon
authors.forename: Toshihide
authors.initials: T
authors.lastname: Oizumi
authors.forename: Shigeru
authors.initials: S
authors.lastname: Karasawa
authors.forename: Wataru
authors.initials: W
authors.lastname: Kaino
authors.forename: Kaoru
authors.initials: K
authors.lastname: Takase
authors.forename: Kyouko
authors.initials: K
authors.lastname: Tada
authors.forename: Yumi
authors.initials: Y
authors.lastname: Jimbu
authors.forename: Kiriko
authors.initials: K
authors.lastname: Wada
authors.forename: Wataru
authors.initials: W
authors.lastname: Kameda
authors.forename: Shinji
authors.initials: S
authors.lastname: Susa
authors.forename: Masaaki
authors.initials: M
authors.lastname: Muramatsu
authors.forename: Isao
authors.initials: I
authors.lastname: Kubota
authors.forename: Sumio
authors.initials: S
authors.lastname: Kawata
authors.forename: Takeo
authors.initials: T
authors.lastname: Kato
mesh_terms: D000368:Aged; D015992:Body Mass Index; D051152:Clusterin / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000235:genetics; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics / Q000502:physiology; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051152:Clusterin; D007328:Insulin