先天性心疾患リスクに対するAKTセリン/スレオニンキナーゼ1多型と環境の複合効果。症例対照研究

Combined effects of AKT serine/threonine kinase 1 polymorphisms and environment on congenital heart disease risk: A case-control study.

• Jianxun Zhao
• Zhi Zeng

抄録

本研究では、AKTセリン/スレオニンキナーゼ1(AKT1)多型と先天性心疾患(CHD)リスクとの複合的な関連性を検討するとともに、AKT1多型の単独多型がCHDに及ぼす役割についても解析した。臨床データと遺伝子型、2群間の対立遺伝子をχ検定で比較し、対照群の遺伝子型分布をHardy-Weinberg equilibriumで確認した。AKT1の3つの多型（rs1130214, rs2494732, rs3803300）において、rs1130214のGT/TT遺伝子型は、症例と対照群で有意な頻度差（P"Zs_200A"="Zs_200A"．04）、AAと比較してCHD発症リスクが1.71倍（OR"Zs_200A"="Zs_200A"1.71、95%CI"Zs_200A"="Zs_200A"1.02-2.86）、T対立遺伝子はキャリアのリスクが1.63倍（OR"Zs_200A"="Zs_200A"1.63、95%CI"Zs_200A"="Zs_200A"1.05-2.54）であった。同様に、rs3803300 GG遺伝子型とG対立遺伝子の両方とも、症例群と対照群の間で明らかな差があり（P"Zs_200A"<"Zs_200A".05）、CHD感受性と密接に関連していた。AKT1 rs1130214, rs3803300多型はCHD感受性の増加と関連していることが明らかになった。環境因子とAKT1多型との相互作用が認められた。この結論を検証するためには、さらなる研究が必要である。

This study aimed to explore the combined association between AKT serine/threonine kinase 1 (AKT1) polymorphisms and congenital heart disease (CHD) risk, meanwhile, the role of AKT1 single polymorphism on CHD was also analyzed.In the first, AKT1 polymorphisms were genotyped in 130 CHD patients and 145 healthy people with the way of polymerase chain reaction-direct sequencing. The clinical data and genotypes, alleles between 2 groups were compared by χ test and the genotype distributions in the control group were checked by Hardy-Weinberg equilibrium. The relative risk strength of disease based on genetic variant was revealed using odds ratio (OR) with 95% confidence interval (95%CI).In 3 polymorphisms of AKT1 (rs1130214, rs2494732, rs3803300), the GT/TT genotype of rs1130214 in cases and controls had a significant frequency difference (P = .04) and was 1.71 times risk developing CHD, compared with AA (OR = 1.71, 95%CI = 1.02-2.86), and T allele had 1.63 times risk for carriers (OR = 1.63, 95%CI = 1.05-2.54). Similarly, both rs3803300 GG genotype and G allele had obvious differences between case and control groups (P < .05) and it was closely associated with CHD susceptibility. At the same time, the combined effects of rs1130214, rs3803300 and family history, smoking were found in our study.AKT1 rs1130214, rs3803300 polymorphisms are associated with the increased susceptibility to CHD. Environmental factors are found the interaction with AKT1 polymorphisms. Further study is needed to verify this conclusion.