Background: Although the peroxisome proliferator-activated receptor-γ2 (PPARG2) Pro12Ala gene variant is associated with diabetes mellitus, the associations and interactions 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 multiplex polymerase 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 allele was 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 interaction 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.
背景：: 肥満や脂質代謝に関連する遺伝子のPPARG2の変異型の人で糖尿病のリスクが低いことが分かってきたが、糖尿病の危険因子とPPARG2の遺伝子型がHbA1cに与える影響は十分に検証されていない。そこで、PPARG2の遺伝子の型と糖尿病の危険因子がHbA1c値に及ぼす影響、および交互作用について検討した。
方法：: J-MICC Studyのベースライン調査に参加した40～69歳の男性1281人、女性1356人のデータを用いて横断研究を実施した。遺伝子多型はMultiplex PCR-based Invader assay方法により決定した。男女別に、Pro12Ala多型とHbA1cの関連について、開始時の年齢、エネルギー摂取量、身体活動量、飲酒状況、喫煙状況、BMIで調整し、共分散分析、重回帰分析を行った。
結果：: 女性では、PPARG2遺伝子のPro12Ala型及びAla12Ala型を持つ者はPro12Pro型を持つ者と比較して、HbA1cが有意に低かった。PPARG2がPro/Pro型の人は、加齢や肥満、家族歴があるとHbA1cの上昇がみられたが、Pro/AlaまたはAla/Ala型の人ではみられなかった。女性ではHbA1c値に対しBMIと遺伝子多型による有意な交互作用がみられた。加齢や肥満、家族歴はHbA1c高値と有意な関連がみられたが、PPARG2遺伝子の多型とHbA1c高値の間に有意な関連はみられなかった。
結論：: PPARG2遺伝子のPro12Ala多型は、HbA1cと既知の危険因子の関連に影響を与える可能性があるが、一般集団においてHbA1c高値に対する影響は既知の危険因子に比べて小さかった。