title: The -1438A/G polymorphism in the 5-hydroxytryptamine receptor 2A gene is related to hyperuricemia, increased gamma-glutamyl transpeptidase and decreased high-density lipoprotein cholesterol level in the Japanese population: a prospective cohort study over 5 years.
abstract: This prospective cohort study in Japanese workers examined the relationship between the -1438A/G polymorphism in the 5-hydroxytryptamine receptor 2A gene and the development of positive findings for various life-style-related disorders. This study over the 5-year period, 1997-2002, included observations of several disorders in cohorts ranging between 560-1023 for males and 477-735 for females who had negative findings for each disorder at baseline. The criteria for development of the disorders were: hypertension, systolic blood pressure > or =140 mmHg or dia-stolic blood pressure > or =90 mmHg or taking antihypertensive medication; overweight, body mass index (BMI) > or =25 kg/m(2); obesity, BMI > or =30 kg/m(2); new onset of cerebral stroke; metabolic abnormalities, glycosylated hemoglobin A1c >6.0%, total cholesterol > or =240 mg/dl, high-density lipoprotein cholesterol <40 mg/dl, uric acid >7.0 mg/dl, gamma-glutamyl transpeptidase > or =60 IU/l in males and > or =30 IU/l in females. Pooled logistic regression analyses were performed using the -1438A/G genotype and other potential factors as covariates. The odds ratios to AA genotype were significant for uric acid (GG, 0.52; AG, 0.59), obesity (AG, 0.24) in males and for high-density lipoprotein cholesterol (GG, 0.11; AG, 0.36), gamma-glutamyl transpeptidase (GG, 0.53; AG, 0.62) and total cholesterol (GG, 1.84) in females. The present study is the first prospective cohort investigation to demonstrate that the -1438G allele has a protective effect against the development of a range of cardiovascular and metabolic disorders. This study indicates that the -1438A/G polymorphism is an independent factor for various disorders in the general Japanese population and suggests that targeting of this polymorphism may be beneficial for preventing these disorders in Japan.
authors.affiliation: Department of Occupational and Environmental Medicine (A2), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. suwa@faculty.chiba-u.jp
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Suwazono
authors.forename: Etsuko
authors.initials: E
authors.lastname: Kobayashi
authors.forename: Mirei
authors.initials: M
authors.lastname: Uetani
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Miura
authors.forename: Yuko
authors.initials: Y
authors.lastname: Morikawa
authors.forename: Masao
authors.initials: M
authors.lastname: Ishizaki
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kido
authors.forename: Hideaki
authors.initials: H
authors.lastname: Nakagawa
authors.forename: Koji
authors.initials: K
authors.lastname: Nogawa
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D006801:Humans; D033461:Hyperuricemia / Q000235:genetics*; D007564:Japan; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics*; D005723:gamma-Glutamyltransferase / Q000097:blood*
chemical_list: D008076:Cholesterol, HDL; D044402:Receptor, Serotonin, 5-HT2A; D005723:gamma-Glutamyltransferase