Nonalcoholic fatty liver disease (NAFLD) is the most common cause of abnormal hepatic steatosis in the absence of a history of alcohol use and with a prevalence of 15%-45% in developed nations. Nonalcoholic steatohepatitis (NASH) is an advanced stage of NAFLD with a pronounced major inflammatory component. The aim of this study was to investigate the possible role of nicotinamide-N-methyltransferase (NNMT) gene rs694539 variant in the development of NASH. Therefore, we analyzed 80 NASH patients and 183 healthy controls using a polymerase chain reaction-restriction fragment length polymorphism method developed in our laboratory. The NNMT rs694539 variant was found to be significantly associated with NASH (χ(2)=9.349, p=0.009). The individuals with the GG genotype had protection against NASH (χ(2)=3.793, p=0.051, odds ratio [OR]=0.580, 95% confidence interval [CI]=0.334-1.006), whereas the individuals with the AA genotype showed statistically significant increased risk for NASH (χ(2)=7.748, p=0.005, OR=7.338, 95% CI=1.448-37.190). Moreover, the G allele was protective against NASH (χ(2)=7.748, p=0.005, OR=0.136, and 95% CI=0.027-0.691). On the other hand, the A allele was a risk factor for NASH (χ(2)=3.793, p=0.051, OR=1.725, and 95% CI=0.994-2.996). Consequently, the rs694539 variant of NNMT gene is a genetic risk factor for developing NASH.

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Studies have revealed that elevated homocysteine levels can cause damage to motor neurons through multiple neurotoxic mechanisms, thus leading to the pathogenesis of amyotrophic lateral sclerosis (ALS). One way by which homocysteine levels are increased in the body is the consequence of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms. Therefore, to address this question, we studied the MTHFR C677T and A1298C polymorphisms in 437 sporadic ALS (SALS) and 439 healthy controls to learn whether they were associated with SALS. The overall SALS were not associated with MTHFR C677T and A1298C polymorphisms (χ(2)=1.378; p=0.502; χ(2)=1.304; p=0.521, respectively). However, when we stratified results in terms of gender, we found that the MTHFR C677T polymorphism (χ(2)=6.376; p=0.041), T677T genotype (χ(2)=5.508; p=0.019; odds ratio [OR]=2.561; 95% confidence interval [CI]=1.142-5.744), C677C/A1298A (χ(2)=5.216; p=0.022; OR=0.424, 95% CI=0.199-0.900), and T677T/A1298A (χ(2)=6.639; p=0.010; OR=2.900; 95% CI=1.252-6.717) compound genotypes were associated with SALS in female patients only. Moreover, stratification of SALS according to the onset of disease indicated that there was no association between MTHFR C677T (χ(2)=1.565; p=0.457; A1298C χ(2)=3.461; p=0.177) polymorphisms and overall spinal onset SALS. Further stratification analysis according to gender revealed that there was a remarkable association between MTHFR C677T (χ(2)=9.728, p=0.008), T677T genotype (χ(2)=7.820; p=0.005; OR=3.126; 95% CI=1.361-7.178) and T allele (χ(2)=5.000; p=0.025; OR=1.711; 95% CI=1.067-2.745), and T677T/A1298A compound genotype (χ(2)=9.108; p=0.003; OR=3.540; 95% CI=1.494-8.387) and spinal onset female SALS only. Likewise, there was also association between MTHFR A1298C polymorphism (χ(2)=5.946; p=0.051) and the C1298C genotype (χ(2)=5.282; p=0.022; OR=2.524; 95% CI=1.125-5.658), and the C677T/C1298C compound genotype (χ(2)=7.155; p=0.007; OR=1.045; 95% CI=0.983-1.112) and bulbar onset SALS only in women. In conclusion, the evidence we provide here clearly shows that MTHFR C677T and A1298C polymorphisms are genetic risk factors for SALS in women in a gender-specific manner whether they are of spinal or bulbar onset.

The original ZNF804A rs1344706 risk variant was identified through genome-wide association studies as a risk factor for schizophrenia. Follow-up studies involving meta-analysis have confirmed that rs1344706 is a risk factor for schizophrenia as well as bipolar disorders. We describe here a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method to genotype ZNF804A rs1344706 variant in patients with schizophrenia. We generated a 220 bp fragment through PCR and subsequently cleaved it by the restriction endonuclease BsaBI, creating two fragments of 114 and 106 bp. Upon change in the nucleotide from T to G, the 106 bp fragment is further cleaved by BsaBI, thus creating two fragments of 87 and 19 bp. As a result, when the 220 bp fragment is cleaved by BsaBI restriction endonuclease, the TT genotype yields two fragments of 114 and 106 bp, and TG genotype four fragments of 114, 106, 87, and 19 bp, and the GG genotype three fragments of 114, 87, and 19 bp. Thus, this is a simple, fast, and cost-effective method to genotype the ZNF804A rs1344706 risk variant. Using this method, we were able to replicate an association between ZNF804A rs1344706 variant and schizophrenia in a Turkish population. Stratification analysis of the population according to the gender showed an association that was statistically significant among overall schizophrenia and male schizophrenia and the risk T allele and TT genotype of the ZNF804A gene.

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