No heart attacks! The blatant gene mutation in Limone sul Garda

From our editorial team

The blue waters of Lake Garda, lemon trees on the slopes, palm trees on the shore: 1,200 people live in Limone sul Garda, with up to 10,000 visitors a day in the high season - yet for centuries the village between the mountains and the lake was barely accessible to outsiders.

The remoteness of Limone sul Garda has had a drastic effect on the local marriage market: due to a lack of choice, locals can only marry within their (extended) family - with consequences! Over the centuries, a super gene has developed due to the limited genetics: those who have it are immune to heart attacks and strokes.

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The super gene is discovered by chance in 1974. Valerio Dagnoli from Limone sul Garda consults the Milanese doctor Cesare Sirtori because of severe abdominal pain. The doctor discovers that Dagnoli has extremely high fat levels in his blood, but low HDL (high density lipoprotein). The HDL protein removes excess cholesterol from the blood vessels. A medical mystery: Dagnoli should have had a heart attack or stroke a long time ago, but he has no cholesterol deposits.

**A holiday dream in blue: Limone sul Garda**
*^{_{Photo: Ana Tramont/500px /Getty Images via canva.com}}*

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The Lion Heart from Limone

The doctor spent five years researching with colleagues to get to the bottom of the mystery, before Cesare Sirtori and his team discovered an HDL cholesterol that protects the blood vessels, now known as "apolipoprotein A1-Milano" (Apo A-1). Of the 243 amino acids of the protein, only the 173rd amino acid of the affected people from Limone differs from that of other people.

limone sul garda on lake garda — **The village with the lion's heart!**
*^{_{Photo onairda/getty images via canva.com}}*

The special protein is an efficient "rinser" of the blood vessels, which makes heart attacks or strokes practically impossible. All gene carriers are descended from a single couple from Limone sul Garda, Cristoforo Pomaroli and Rosa Giovanelli, who married in the first half of the 17th century. The appearance of the protein can be traced back to 1644. Today, around 5 per cent of locals still have the gene mutation.