Haplotype-based case-control study of calpain (CAPN2) gene and hypertensive disorders of pregnancy
Various theories have been developed regarding the pathology and etiology of hypertensive disorders of pregnancy (HDP). The impaired placenta secretes antiangiogenic factors into maternal blood, resulting in the development of pregnancy-induced hypertension (PIH). Both µ-calpain and m-calpain are proteins known to be involved in placentation, with the catalytic subunits encoded by the CAPN1 and CAPN2 genes, respectively. The purpose of this study was to find disease susceptibility genes for PIH by conducting an association analysis for HDP using specific gene markers comprising individual single nucleotide variants (SNVs) and haplotypes within the CAPN2 gene. We selected five SNVs in the human CAPN2 gene and performed an association study with 95 HDP patients and 177 age-matched non-HDP subjects. In the analyses conducted for the CAPN2 SNVs, the recessive model of rs1153968 differed significantly between the gestational hypertension (GH, a category of HDP) and control groups. However, rs1153968 deviated from Hardy-Weinberg equilibrium and was deemed unlikely to be a significant factor. No significant differences were seen in any of the other SNVs analyzed. However, association analyses involving the rs1892077-rs98041140-rs17599-rs1153954 haplotype in the CAPN2 gene haplotypes revealed that G-A-A-T was found at a significantly lower frequency, and G-A-C-T and G-G-A-A at significantly greater frequencies, in patients with PIH. These findings may be useful in preventing PIH onset, as well as for the early discovery and treatment of patients who are carriers of the haplotype likely to be associated with this condition.