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.
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.
Suwazono
Yasushi
Y
Department of Occupational and Environmental Medicine (A2), Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan. suwa@faculty.chiba-u.jp
Kobayashi
Etsuko
E
Uetani
Mirei
M
Miura
Katsuyuki
K
Morikawa
Yuko
Y
Ishizaki
Masao
M
Kido
Teruhiko
T
Nakagawa
Hideaki
H
Nogawa
Koji
K
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*
D008076:Cholesterol, HDL; D044402:Receptor, Serotonin, 5-HT2A; D005723:gamma-Glutamyltransferase