John (and possibly Sherlock, too, who has failed to deduce it before ('There's always something!')) learns that Greg and Mycroft used to be lovers many years ago. They used to be in love with each other, but it ended very badly, with a major heartbreak and with Greg later marrying a woman.

Maybe Greg and Mycroft hadn't seen each other for a long time afterwards, until Sherlock was arrested for drugs by Greg, who probably failed to recognise the dirty junkie as Mycroft's younger brother.

Somehow John and Sherlock find out. Maybe tipsy Greg becomes talkative in a pub with John. And maybe the past still hurts.