Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population

Megumi Hara, Yasuki Higaki, Naoto Taguchi, Koichi Shinchi, Emi Morita, Mariko Naito, Nobuyuki Hamajima, Naoyuki Takashima, Sadao Suzuki, Akihiko Nakamura, Ohnaka Keizo, Hirokazu Uemura, Hideki Nishida, Satoyo Hosono, Haruo Mikami, Michiaki Kubo, Hideo Tanaka

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Abstract

Background: Although the peroxisome proliferator-activated receptor-Γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations andinteractions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions. Methods: This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplepolymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI],energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. Results: After adjustment, the Ala allelewas significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes.When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interactio of genotype and BMI on HbA1c was observed in women. Older age,BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not. Conclusions: Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level,it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.

Original languageEnglish
Pages (from-to)523-531
Number of pages9
JournalJournal of epidemiology
Volume22
Issue number6
DOIs
Publication statusPublished - Nov 20 2012

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Diabetes Mellitus
Body Mass Index
Genotype
Population
Alleles
Social Adjustment
Peroxisome Proliferator-Activated Receptors
Confounding Factors (Epidemiology)
Glycosylated Hemoglobin A
Energy Intake
Linear Models
Japan
Cohort Studies
Cross-Sectional Studies
Smoking
Alcohols
Exercise
Polymerase Chain Reaction
Genes

All Science Journal Classification (ASJC) codes

  • Epidemiology

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Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population. / Hara, Megumi; Higaki, Yasuki; Taguchi, Naoto; Shinchi, Koichi; Morita, Emi; Naito, Mariko; Hamajima, Nobuyuki; Takashima, Naoyuki; Suzuki, Sadao; Nakamura, Akihiko; Keizo, Ohnaka; Uemura, Hirokazu; Nishida, Hideki; Hosono, Satoyo; Mikami, Haruo; Kubo, Michiaki; Tanaka, Hideo.

In: Journal of epidemiology, Vol. 22, No. 6, 20.11.2012, p. 523-531.

Research output: Contribution to journalArticle

Hara, M, Higaki, Y, Taguchi, N, Shinchi, K, Morita, E, Naito, M, Hamajima, N, Takashima, N, Suzuki, S, Nakamura, A, Keizo, O, Uemura, H, Nishida, H, Hosono, S, Mikami, H, Kubo, M & Tanaka, H 2012, 'Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population', Journal of epidemiology, vol. 22, no. 6, pp. 523-531. https://doi.org/10.2188/jea.JE20120078
Hara, Megumi ; Higaki, Yasuki ; Taguchi, Naoto ; Shinchi, Koichi ; Morita, Emi ; Naito, Mariko ; Hamajima, Nobuyuki ; Takashima, Naoyuki ; Suzuki, Sadao ; Nakamura, Akihiko ; Keizo, Ohnaka ; Uemura, Hirokazu ; Nishida, Hideki ; Hosono, Satoyo ; Mikami, Haruo ; Kubo, Michiaki ; Tanaka, Hideo. / Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population. In: Journal of epidemiology. 2012 ; Vol. 22, No. 6. pp. 523-531.
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abstract = "Background: Although the peroxisome proliferator-activated receptor-Γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations andinteractions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions. Methods: This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplepolymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI],energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. Results: After adjustment, the Ala allelewas significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes.When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interactio of genotype and BMI on HbA1c was observed in women. Older age,BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7{\%} NGSP), whereas PPARG2 polymorphism was not. Conclusions: Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level,it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.",
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T1 - Effect of the PPARG2 Pro12Ala polymorphism and clinical risk factors for diabetes mellitus on HbA1c in the Japanese general population

AU - Hara, Megumi

AU - Higaki, Yasuki

AU - Taguchi, Naoto

AU - Shinchi, Koichi

AU - Morita, Emi

AU - Naito, Mariko

AU - Hamajima, Nobuyuki

AU - Takashima, Naoyuki

AU - Suzuki, Sadao

AU - Nakamura, Akihiko

AU - Keizo, Ohnaka

AU - Uemura, Hirokazu

AU - Nishida, Hideki

AU - Hosono, Satoyo

AU - Mikami, Haruo

AU - Kubo, Michiaki

AU - Tanaka, Hideo

PY - 2012/11/20

Y1 - 2012/11/20

N2 - Background: Although the peroxisome proliferator-activated receptor-Γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations andinteractions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions. Methods: This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplepolymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI],energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. Results: After adjustment, the Ala allelewas significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes.When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interactio of genotype and BMI on HbA1c was observed in women. Older age,BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not. Conclusions: Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level,it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.

AB - Background: Although the peroxisome proliferator-activated receptor-Γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations andinteractions of this polymorphism and known clinical risk factors with glycated hemoglobin (HbA1c) remain poorly understood. We investigated if carrying the Ala allele was inversely associated with HbA1c level and examined possible interactions. Methods: This cross-sectional analysis used data collected from 1281 men and 1356 women aged 40 to 69 years who completed the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. PPARG2 polymorphism was determined by multiplepolymerase chain reaction (PCR)-based Invader assay. Multiple linear regression and ANCOVA were used to control for confounding variables (age, body mass index [BMI],energy intake, alcohol, smoking, physical activity, and family history of diabetes) and examine possible interactions. Results: After adjustment, the Ala allelewas significantly inversely associated with HbA1c in women but not in men. Older age, BMI, and family history of diabetes were associated with higher HbA1c in both sexes.When stratified by PPARG2 genotype, these associations were observed in subjects with the Pro12Pro genotype but not in Ala allele carriers. A significant interactio of genotype and BMI on HbA1c was observed in women. Older age,BMI, and family history of diabetes were significantly associated with high-normal HbA1c (≥5.7% NGSP), whereas PPARG2 polymorphism was not. Conclusions: Although PPARG2 Pro12Ala polymorphism might attenuate associations between known risk factors and HbA1c level,it had a small effect on high-normal HbA1c, as compared with clinical risk factors, in the general population.

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