D. Southerners cited tariffs protecting domestic industries as a major grievance against the United States government
Explanation:
The factor that most supports the idea that regional economic differences were a major cause of the civil war is "Southerners cited tariffs protecting domestic industries as a major grievance against the United States government."
The above statement shows that southerners were complaining about tariffs is favoring the northern region because it protects domestic industries. The northern region of the United States has an economy based on industries in which tariff is protecting for them, however, the Southerners don't like that situation.