The irony of coal mining
It's a job, sure, but besides the meager pay, coal mining has another negative side: cancer. By saying yes to a safe life as a coal miner, a man condemns himself to worse fates than unemployment—black lung and then, on top of it all, the mine closes down and everyone loses their job. Some job.
Religion in the Bible Belt
Sometimes, religion can be used as a way of coping with a difficult life, but what about when that life is hopeless? Then, often, people's desperations drive them to become hyper-religious, and a systemic injustice begins—the religious majority suppressing the non-believers. It's depicted in the novel in the character of Andrew.
The irony of God
How could there be a good, all-knowing God who lets entire towns come to their demise? A God who allows the wrongful injustices that are depicted in the novel? For Ruth, it's a sacrilege to ask the question, but the question is obvious, given the desperation of their situation. It's Ruth's inability to be honest with herself about the state of affairs that keeps her from ever taking a step of faith and doing something new. Ironically, her relationship to God is dysfunctional.
The irony of homosexuality
Homosexuality is treated like an evil thing by fundamentalist Christians, which is ironic, because that means that Christians are judging, even when Jesus's instruction was "Don't judge other people." Homosexuality is shown by the novel to be the outcome of repression by a religious person, so if anyone is to blame, it's the abusive, hyper-religious mother herself.
The irony of the gun
An anti-inheritance occurs at the end of the story. Instead of Andrew's parents dying and handing down an heirloom, his mother becomes suicidal and hands down to Andrew his father's loaded gun. She's letting him inherit her suicidal depression and hopelessness, which is ironic, given that she is his mother and was supposed to give life to him. This is an ironic inversion of her earlier claim that giving birth makes her destiny complete. She is undoing her success in that regard, "cursing God," one might say.
