PRDM16, LRP1 and TRPM8 genetic polymorphisms are risk factor for Pakistani migraine patients

Abstract

Background Migraine is a chronic neurovascular condition characterized by recurring attacks of pulsating headaches. Genome-wide association studies (GWAS) identified many potential loci associated with migraine. To check the association of polymorphisms of PRDM16 (rs2651899), LRP1 (rs11172113), and TRPM8 (rs10166942) with migraine, the first time a case-control study was conducted in understudied Pakistani population. Methods The study included 127 migraine patients (21 in migraine with aura and 106 with migraine without aura group) and 120 healthy control subjects from different areas of Punjab, Pakistan. Blood samples were collected from all the participants, and DNA was isolated from the lymphocytes by the modified organic method. Sanger’s sequencing was done for PRDM16 ( rs2651899), LRP1 (rs11172113), and TRPM8 (rs10166942) in all the samples to check the genotype. Logistic regression analysis was done using SPSS 20.0 to check the association of these SNPs with migraine susceptibility. Results We found statistically significant differences between case and control group for PRDM16 ( rs2651899) at genotypic level (p < 0.001), allelic level (p < 0.001; OR 3.088; 95% CI 2.082–4.579) and for dominant model (p < 0.001; OR 5.437; 95% CI 3.112–9.498). The major findings of this study suggested that PRDM16 rs2651899 is strongly associated with migraine in overall and subgroup analysis of genotypes. LRP1 (rs11172113) showed significant association with migraine except in subgroup comparison. A similar trend of association was found for TRPM8 (rs10166942) however, significant association was found only at the allelic level but no significant difference was seen at the genotypic level between case and control. One novel mutation c.67 + 4436_67 + 4438delA was also identified in the current study near LRP1 (rs11172113) polymorphic site. Conclusion In this first-ever replication report from Pakistan, PRDM16 ( rs2651899) was found as a potential genetic marker in migraine susceptibility while LRP1 (rs11172113) and TRPM8 (rs10166942) showed partial association in subgroup analysis.

Genetic Factors for Coronary Heart Disease and Their Mechanisms: A Meta-Analysis and Comprehensive Review of Common Variants from Genome-Wide Association Studies

“…Additionally, a study by Xian et al (2017) found that phosphorylation of LDL-related protein 1 (LRP-1) on the macrophage surface could also increase ABCA1 protein expression by activating the LRP-1/SHC1/PI3K/AKT/PPAR-γ/LXR axis [ 78 ]. The rs11172113*C is a common variant of LRP1 that could cause splice site alteration in one of the gene’s exon-intron junctions [ 79 ]. This could result in LRP-1 structural change [ 79 ], which could potentially impair the protein activity.…”

“…The rs11172113*C is a common variant of LRP1 that could cause splice site alteration in one of the gene’s exon-intron junctions [ 79 ]. This could result in LRP-1 structural change [ 79 ], which could potentially impair the protein activity. Since our findings showed that both rs1412444*T ( LIPA ) and rs11172113*C ( LRP1 ) increased CHD risk 1.02-fold ( Table S2 ), we hypothesize that the underlying mechanisms might be related to reduced lipase A enzyme expression and structural variation of the LRP-1 protein that renders it less functional.…”

Cannabis Pharmacogenomics: A Path to Personalized Medicine

“…Moreover, the rs12472151 , rs11562975 , and rs28901637 polymorphisms of the TRPM8 gene were associated with metabolic syndrome, obesity, and cholesterol levels [ 138 , 139 , 140 ]. Variants at TRPM8, rs10166942 , and rs2362290 have been related to slower colonic transit rates, increased risk of irritable bowel syndrome, and chronic migraine [ 141 , 142 ].…”

A replication study separates polymorphisms behind migraine with and without depression

“…Rs2651899 of PRDM16 showed associations in the Women's Genome Health Study (WGHS) with migraine compared to non-migraineurs and also with migraine compared to non-migraine type headache [44]. A replication study on a Chinese population supported a role for rs2651899 as a risk factor in migraine without aura regardless of gender [45] and its role was also demonstrated in two North Indian, a Chinese Han, a Spanish, a Swedish, and a Pakistani population [46][47][48][49][50][51]. A recent meta-analysis also demonstrated an association between rs2651899 and migraine risk [52].…”