* Corresponding author: Narjes Bakhtari Department of Biology Department, Shahid Beheshti University, Tehran, Iran ISSN: 0976-3031 RESEARCH ARTICLE STUDY OF ASSOCIATION BETWEEN 4 DIFFERENT SNPs LOCATED ON CHDH GENE WITH AZOOSPERMIA MALE INFERTILITY IN IRANIAN POPULATION Narjes Bakhtari, Masoud Sheidai, Hamid Gourabi, Zahra Noormohammadi, Esmat Ghalkhani, and Ali Mohammad Malekasgar 1,2,4 Biology Department, Shahid Beheshti University, Tehran, Iran 3 Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Tehran, Iran 5 Department of Medical Science, Genetic Unit, Qom University of Medical Sciences, Iran ARTICLE INFO ABSTRACT Article History: Received 11 th , May, 2014 Received in revised form 16 th , May, 2014 Accepted 14 th , June, 2014 Published online 28 th , June, 2014 Purpose A case-control population study was performed to investigatie the association of the SNPs rs: (12676) and (rs: 9001), (rs: 200569248) and (rs: 78371839) located on CHDH gene with azoospermiamale infertility in Iranian population. Methods Two separated population of Center and North of Iran (In Royan Institute) were collected. DNA was extracted from each samples through salting-out method. a 345bp segment of the gene was amplified using PCR. All samples were genotyped using direct sequencing. Chi-squared test and Odds Ratio were recruited to check the association of the SNPs with azoospermia, and to investigate the genetic difference in populations AMOVA was performed. Result There was no significant genetic difference between our populations, which meant they were almost genetically similar, so we merged data from both populations in one single group. We also find a positive association between SNPs (rs: 12676) and (rs: 9001) and azoospermia infertility but no association was found in SNPs (rs: 200569248) and (rs: 78371839) with azoospermia male infertility. Conclusion Positive association probably reveals an important role of this gene in male infertility. Further studies are needed to support the obtained result. It is important to know if such an association plays a key role in male infertility so probably with a Betaine rich diet treatment we can overcome to the CHDH enzyme defects. © Copy Right, IJRSR, 2014, Academic Journals. All rights reserved. Key words: Infertility. Azoospermia .Choline Dehydrogenase Genetic diversity . INTRODUCTION Infertility is a condition in which a couple cannot conceive after 12 months of attempt [1, 2].About 50% of infertility problems are associated to the male factor [3]. Genetic factors leading to infertility are: chromosomal abnormalities, monogenetic and multifactorial defects as well as genetic endocrine failure [4]. Another major cause of infertility is the impact of destructive environmental factors [5-7]. Methyl folate, methionine and choline are the main source of methyl groups in our diet. [8, 9]. Metabolisms of these micro- nutritions play an essential role in the formation of the S- adenosyl-methionine (SAM), as the general donor of the methyl group. [10]. Key enzymes in methionine metabolism pathway are: phosphatidyl choline N-methyl transferase (PEMT), choline dehydrogenase (CHDH), betaine- homocysteine methyl transferase (BHMT) [11]. CHDH enzyme catalyses the oxidation of choline to betaine using an intermediate molecule called betaine aldehyde [10]. Histological studies revealed that CHDH gene deletion caused a high reducing of betaine. It was shown that CHDH is expressed highly in testis, liver and kidney [11]. Dietary sources of betaine include wheat, shellfish, spinach and sugar beets [12, 13]. In addition, betaine can be made de novo via the oxidation of choline in a series of reactions catalyzed by CHDH and betaine aldehyde dehydrogenase (BADH, EC 1.2.1.8) [14-19]. Sperm Mitochondria is located in the mid piece. Lack of the CHDH enzyme, which is located generally in the inner membrane of mitochondria, can lead to the abnormal shape of it according to the electron microscope studies. In fact, it causes reducing in ATP concentration in mitochondria of the testis [11]. In the present study, molecular diversity of rs: 12676 (G674T), a functional non-synonymous SNP results in the replacement of arginine, a polar, hydrophilic amino acid at position 78 with leucine, The CHDH minor T allele is associated with increased susceptibility to developing clinical symptoms of dietary choline deficiency (steatosis and muscle cell damage) [20] as well as increased risk of breast cancer [21], also SNP, rs: 9001 (A560C) a non-synonymous SNP leads to substitution of glutamate to alanine, a change from medium-size and acidic (E) to small size and hydrophobic (A) at position 40, rs:78371839 (C661T) a non-synonymous SNP results in changing of proline to serine and finally rs:200569248( C673T) which leads to change. Available Online at http://www.recentscientific.com International Journal of Recent Scientific Research International Journal of Recent Scientific Research Vol. 5, Issue, 6, pp. 1222-1225, June, 2014