Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women

Kikuko Hotta, Aya Kitamoto, Takuya Kitamoto, Seiho Mizusawa, Hajime Teranishi, Tomoaki Matsuo, Yoshio Nakata, Hideyuki Hyogo, Hidenori Ochi, Takahiro Nakamura, Seika Kamohara, Nobuyuki Miyatake, Kazuaki Kotani, Ryoya Komatsu, Naoto Itoh, Ikuo Mineo, Jun Wada, Masato Yoneda, Atsushi Nakajima, Tohru FunahashiShigeru Miyazaki, Katsuto Tokunaga, Hiroaki Masuzaki, Takato Ueno, Kazuaki Chayama, Kazuyuki Hamaguchi, Kentaro Yamada, Toshiaki Hanafusa, Shinichi Oikawa, Hironobu Yoshimatsu, Toshiie Sakata, Kiyoji Tanaka, Yuji Matsuzawa, Kazuwa Nakao, Akihiro Sekine

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P0.0018 and 0.0022, respectively) and SFA (P0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.

Original languageEnglish
Pages (from-to)46-51
Number of pages6
JournalJournal of Human Genetics
Volume57
Issue number1
DOIs
Publication statusPublished - Jan 2012

Fingerprint

Intra-Abdominal Fat
Subcutaneous Fat
Genes
Single Nucleotide Polymorphism
Blood Pressure
Hypertension
Genetic Loci
Abdominal Obesity
Genome-Wide Association Study
Dyslipidemias
Type 2 Diabetes Mellitus
Alleles
Tomography
Morbidity
Mortality
Population

Keywords

  • computed tomography
  • CYP17A1
  • Japanese subjects
  • NT5C2
  • sexual dimorphism
  • subcutaneous fat area
  • visceral fat area

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics

Cite this

Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women. / Hotta, Kikuko; Kitamoto, Aya; Kitamoto, Takuya; Mizusawa, Seiho; Teranishi, Hajime; Matsuo, Tomoaki; Nakata, Yoshio; Hyogo, Hideyuki; Ochi, Hidenori; Nakamura, Takahiro; Kamohara, Seika; Miyatake, Nobuyuki; Kotani, Kazuaki; Komatsu, Ryoya; Itoh, Naoto; Mineo, Ikuo; Wada, Jun; Yoneda, Masato; Nakajima, Atsushi; Funahashi, Tohru; Miyazaki, Shigeru; Tokunaga, Katsuto; Masuzaki, Hiroaki; Ueno, Takato; Chayama, Kazuaki; Hamaguchi, Kazuyuki; Yamada, Kentaro; Hanafusa, Toshiaki; Oikawa, Shinichi; Yoshimatsu, Hironobu; Sakata, Toshiie; Tanaka, Kiyoji; Matsuzawa, Yuji; Nakao, Kazuwa; Sekine, Akihiro.

In: Journal of Human Genetics, Vol. 57, No. 1, 01.2012, p. 46-51.

Research output: Contribution to journalArticle

Hotta, K, Kitamoto, A, Kitamoto, T, Mizusawa, S, Teranishi, H, Matsuo, T, Nakata, Y, Hyogo, H, Ochi, H, Nakamura, T, Kamohara, S, Miyatake, N, Kotani, K, Komatsu, R, Itoh, N, Mineo, I, Wada, J, Yoneda, M, Nakajima, A, Funahashi, T, Miyazaki, S, Tokunaga, K, Masuzaki, H, Ueno, T, Chayama, K, Hamaguchi, K, Yamada, K, Hanafusa, T, Oikawa, S, Yoshimatsu, H, Sakata, T, Tanaka, K, Matsuzawa, Y, Nakao, K & Sekine, A 2012, 'Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women', Journal of Human Genetics, vol. 57, no. 1, pp. 46-51. https://doi.org/10.1038/jhg.2011.127
Hotta, Kikuko ; Kitamoto, Aya ; Kitamoto, Takuya ; Mizusawa, Seiho ; Teranishi, Hajime ; Matsuo, Tomoaki ; Nakata, Yoshio ; Hyogo, Hideyuki ; Ochi, Hidenori ; Nakamura, Takahiro ; Kamohara, Seika ; Miyatake, Nobuyuki ; Kotani, Kazuaki ; Komatsu, Ryoya ; Itoh, Naoto ; Mineo, Ikuo ; Wada, Jun ; Yoneda, Masato ; Nakajima, Atsushi ; Funahashi, Tohru ; Miyazaki, Shigeru ; Tokunaga, Katsuto ; Masuzaki, Hiroaki ; Ueno, Takato ; Chayama, Kazuaki ; Hamaguchi, Kazuyuki ; Yamada, Kentaro ; Hanafusa, Toshiaki ; Oikawa, Shinichi ; Yoshimatsu, Hironobu ; Sakata, Toshiie ; Tanaka, Kiyoji ; Matsuzawa, Yuji ; Nakao, Kazuwa ; Sekine, Akihiro. / Genetic variations in the CYP17A1 and NT5C2 genes are associated with a reduction in visceral and subcutaneous fat areas in Japanese women. In: Journal of Human Genetics. 2012 ; Vol. 57, No. 1. pp. 46-51.
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AU - Mizusawa, Seiho

AU - Teranishi, Hajime

AU - Matsuo, Tomoaki

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AU - Miyatake, Nobuyuki

AU - Kotani, Kazuaki

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AU - Itoh, Naoto

AU - Mineo, Ikuo

AU - Wada, Jun

AU - Yoneda, Masato

AU - Nakajima, Atsushi

AU - Funahashi, Tohru

AU - Miyazaki, Shigeru

AU - Tokunaga, Katsuto

AU - Masuzaki, Hiroaki

AU - Ueno, Takato

AU - Chayama, Kazuaki

AU - Hamaguchi, Kazuyuki

AU - Yamada, Kentaro

AU - Hanafusa, Toshiaki

AU - Oikawa, Shinichi

AU - Yoshimatsu, Hironobu

AU - Sakata, Toshiie

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N2 - Visceral fat accumulation has an important role in increasing the morbidity and mortality rates, by increasing the risk of developing several metabolic disorders, such as type 2 diabetes, dyslipidemia and hypertension. New genetic loci that are associated with increased systolic and diastolic blood pressures have been identified by genome-wide association studies in Caucasian populations. This study investigates whether single nucleotide polymorphisms (SNPs) that confer susceptibility to high blood pressure are also associated with visceral fat obesity. We genotyped 1279 Japanese subjects (556 men and 723 women) who underwent computed tomography for measuring the visceral fat area (VFA) and subcutaneous fat area (SFA) at the following SNPs: FGF5 rs16998073, CACNB2 rs11014166, C10orf107 rs1530440, CYP17A1 rs1004467, NT5C2 rs11191548, PLEKHA7 rs381815, ATP2B1 rs2681472 and rs2681492, ARID3B rs6495112, CSK rs1378942, PLCD3 rs12946454, and ZNF652 rs16948048. In an additive model, risk alleles of the CYP17A1 rs1004467 and NT5C2 rs11191548 were found to be significantly associated with reduced SFA (P0.00011 and 0.0016, respectively). When the analysis was performed separately in men and women, significant associations of rs1004467 (additive model) and rs11191548 (recessive model) with reduced VFA (P0.0018 and 0.0022, respectively) and SFA (P0.00039 and 0.00059, respectively) were observed in women, but not in men. Our results suggest that polymorphisms in the CYP17A1 and NT5C2 genes influence a reduction in both visceral and subcutaneous fat mass in Japanese women.

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KW - Japanese subjects

KW - NT5C2

KW - sexual dimorphism

KW - subcutaneous fat area

KW - visceral fat area

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