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During infancy, orienting and gaze aversion serve as major self-regulatory mechanisms and play an important role in the development of deliberate self-regulation and control. The present study examined the interaction of intrinsic factors (MAOA-uVNTR and 5-HTTLPR gene polymorphisms) and extrinsic factors (maternal sensitivity) on early infant self-regulatory behavior. We assessed 5-HTTLPR (ss + sl versus ll) and MAOA-uVNTR (3 and 4 among boys, and 3/3, 3/4, and 4/4 among girls) polymorphisms, determined maternal sensitivity during mother–child free play, and coded infant self-regulatory behavior (i.e., orienting shifts in a temperament test) in 281 six-month-old infants. We found that infants who experienced a lower level of maternal sensitivity and had the short allele of 5-HTTLPR variants and the 3/3 MAOA-uVNTR polymorphism displayed lower self-regulation capacity than did those infants with a higher level of maternal sensitivity. This finding suggested a modulatory role of maternal sensitivity. Moreover, these findings are consistent with the genetic vulnerability hypothesis, which states that beneficial environmental factors serve as a buffer against harmful genetic predispositions during child development. [ABSTRACT FROM AUTHOR]