Most extensively studied human progesterone receptor polymorphic variant [PMID 22722322] affecting both transcription factors PR-A and PR-B. PROGINS is characterized by V660L SNP rs1042838 in exon 4, one silent H770H SNP rs1042839 in exon 5 and intronic 320-bp PV/HS-1 Alu insertion between exon 7 and 8, in complete linkage disequilibrium (allele frequency in Caucasians 9-19%). Any of these three alleles appear to uniquely identify the presence of the other two. Minor allele rs1042838(T) is usually used to tag the presence of this allele. Should indicate haplotype gs287.
Recent 2014 meta-analysis backed association of PROGINS allele with ovarian cancer in caucasians, those never having used oral contraceptives, and serous (endometrial) tumor cases, although concludes more detailed and well-designed studies are still needed. Another meta-study [PMID 24943061] looking at endometrial cancer specifically found association (OR 1.52-2.72, p = 0.0008-0.03) among European women in particular. Apparent flip-flop phenomenon seen in Brazilian group supports conclusion of some papers that rs1042838 may not be the causal variant, but in close linkage disequilibrium with it.
As of early 2015, Google Scholar search for PROGINS brings up nearly 700 published articles including possible association with additional conditions from late onset migraine [PMID 25494303] by delaying migraine onset to hyperprolactinaemia [PMID 15807882].
[PMID 24943061] Association of the progesterone receptor gene polymorphism (PROGINS) with endometriosis: a meta-analysis.
[PMID 24197980] Progesterone receptor PROGINS and +331G/A polymorphisms confer susceptibility to ovarian cancer: a meta-analysis based on 17 studies.
[PMID 22722322] Progesterone receptor variants associated with the PROGINS haplotype exhibit functional properties similar to those of wild-type progesterone receptor.
[PMID 17293450] The PROGINS polymorphism of the human progesterone receptor diminishes the response to progesterone.
[PMID 15632380] Clarifying the PROGINS allele association in ovarian and breast cancer risk: a haplotype-based analysis.