Abstract:

BACKGROUND: The β3-adrenoceptor (ADRB3) gene Trp64Arg polymorphism has been shown to be associated with obesity as well as type 2 diabetes and cardiovascular disease. The incidence of overweight and the risks of type 2 diabetes and cardiovascular disease are also increased in major depression and schizophrenia. We hypothesized that the Trp64Arg polymorphism may be associated with increased risk of schizophrenia and depression.
METHODS: The Trp64Arg was genotyped in 504 patients with schizophrenia, 650 with major depressive disorder (MDD), and 1170 healthy controls. Of these participants, body mass index (BMI) data were available for 125 patients with schizophrenia, 219 with MDD, and 261 controls.
RESULTS: No significant difference in genotype or allele distribution was found across the diagnostic groups. No significant difference in BMI was observed between the Arg allele carriers and the non-carriers in the MDD and the control groups. However, patients with schizophrenia carrying the Arg allele had significantly higher BMI (Mean (SD): Arg carriers: 26.5 (6.9), Arg non-carriers: 23.8 (4.3); P=0.019) and a higher rate of being overweight (BMI of 25 or more) compared to their counterparts (Trp/Trp group) (% overweight (SE): Arg carriers: 52.3 (7.5), Arg non-carriers: 32.1 (5.2); P=0.027).
CONCLUSIONS: We obtained no evidence for the association of ADRB3 Trp64Arg with the development of MDD or schizophrenia. However, the Arg allele was found to be associated with higher BMI and being overweight in patients with schizophrenia. This may imply that genotyping ADRB3 is of clinical use to detect schizophrenic individuals at risk for developing obesity.

日本語要旨:

β3アドレナリン受容体遺伝子(ADRB3)Trp64Arg多型は肥満、2型糖尿病、心血管系疾患に関連することが過去に報告されている。これらの疾患のリスクは、一般人口よりもうつ病や統合失調症の患者において高いことから、我々はTrp64Argがうつ病や統合失調症にも関連している可能性があると考え、関連研究を行った。統合失調症患者504名、大うつ病性障害患者650名、健常者1170名に対しTrp64Argのタイピングを行ったが、遺伝子型およびアレル頻度は、各群間において統計学的に有意差を認めず、Trp64Argと統合失調症およびうつ病との関連を示すことはできなかった。一方で、body mass index (BMI)が記録されていた125名の統合失調症患者において、Argアレル保有者は非保有者と比較して平均BMIが有意に高く(保有者：26.5±6.9, 非保有者：23.8±4.3; P = 0.019)、肥満(BMI ≧ 25)の率も有意に高かった(保有者：52.3±7.5 (%), 非保有者：32.1±5.2 (%); P = 0.027)。