Preterm delivery and gestational hypertension, both are critical abnormalities in new born, the etiology still not elucidated. Nor available treatment so far. How this reality perceived?

In my previous blog message, I mentioned responsible gene for gestational hypertension has been identified by US scientists. In fact, two proteinases were included in the list of responsible candidate genes with which, my NPO has been established on, namely P-LAP and A-LAP.

I gave explanation to P-LAP in the past blog messages, therefore, most of you who have been visited to my blog should know about this. For A-LAP, I shall give some detail explanation in the future coming blog messages.

Jeffrey C Murray from Iowa University reported the fact that, P-LAP is suspected as a responsible gene for preterm delivery, inferred from genetic search of preterm newborns and their mothers in the US, Finland, Denmark and, Argentina. (reference 1)

Rather sophisticated method namely, QTL analysis (quantitative trait genetic loci verification), was employed for gene identification. This time also, used SNP analysis, another sophisticated method of gene analysis. For this, I will explain about DNA.

DNA is the nucleic acid (acidic chemical substance) which contains a sugar substance called deoxyribose thus, named deoxyribo-nucleic acid.

The basic, minimal, unit of DNA comprised of base, sugar (deoxiribose),phosphate. And the unit is called nucleotide. The minimal units are connected each other mediated by phosphoric acid forming a chain-like structure.

Bases are then connected each other forming a double helix structure.


There are four different bases namely, adenine(A), guanine(G), cytosine(C), and thymine(T). One of these is combined to the fundamental unit of DNA, with a dogmatic mechanism that A and T or G and C are combined together. Thus, combination of two chains always on these two bases.

The sequence of these bases ciphers genetic configuration of the livings. SNP means a single base polymorphism, in other words, only one unit of the base is different from the common base sequence but, it will cause different phenotype.

It is estimated that one in thousand bases in human DNA has SNP. Most of SNP exist outside of the protein synthesis controlling domain, thereby not exerting phenotype characteristics  but SNPs that affect within gene controlling domain are thought to dictate individual genetic characteristics.

In short, SNP is an indicator for susceptibility of polygenetic disorders such as hypertension or diabetes, and individual reactions to the drugs (efficacy and adverse reactions), or even the basic body constitution. By analyzing SNP, it is hoped that the wide scope of tailor-made or prognostic medicine may become in reality.

In Murray’s literature, the following explanation were given inferring P-LAP may be a responsible gene for preterm labor. Also, details of the results of the experiments using P-LAP knock-out mice are explained, which are published by Nagoya University chair sponsored by Mr.Akira Yamamoto Gudmann KK for five years after my retirement.(reference 2)

Inflammation related or immunology related genes have been investigated in relation to preterm labor, however, these efforts could not identify the culprit. The researchers analyzed SNP of oxytocin metabolizing related genes which is obviously the critical hormone for uterine contraction in pregnant women.

These genes are oxytocin, oxytocin receptor, oxytocin degrading enzyme i.e., P-LAP. As a result of SNP analysis, the only substance that had related to preterm labor was P-LAP gene of the mother.

In 2009, we reported the fact that oxytocin sensitivity (uterine contractile) was increased and, gestation period was shortened in the P-LAP gene knockout pregnant mice. (reference ) They also mentioned that their study results were consistent with the results of our clinical study of several delivery cases which suggested that maternal P-LAP fluctuation could predict the onset of labor in pregnant healthy women. (reference 3)


1.Kim J et al. BMC Medical Genetics 2013;14:77      

2. Ishii M et al. Life Sciences 2009; 84:668

3.Mizutani S et al. Clin Biochem 1982;15:141