PNPLA2 and heart failure: Furthermore, estrogen appears to have a protective effect in patients carrying the PNPLA2 mutation since heart failure has been reported in almost 20% of NLSDM female patients and 55% of male patients, although the frequency of PNPLA2 mutations that cause a lack of ATGL protein production or expression of truncated proteins is similar in men and women (Higashi et al., 2015; Missaglia et al., 2017).